Adaptive deep brain stimulation using homeostatic window

ABSTRACT

Techniques are disclosed for defining a homeostatic window for controlling delivery of electrical stimulation therapy to a patient. In one example, a method includes generating and delivering electrical stimulation therapy to tissue of a patient via electrodes. Further, the method includes adjusting a level of a parameter of the electrical stimulation therapy such that a signal of the patient is not less than a lower bound and not greater than an upper bound. The lower bound is determined to be the magnitude of the signal while receiving electrical stimulation therapy sufficient to reduce one or more symptoms of a disease while the patient was receiving medication for reduction of the one or more symptoms. Further, the upper bound is determined to be the magnitude of the signal while receiving electrical stimulation therapy sufficient to reduce the one or more symptoms when the patient was not receiving the medication.

This application is a divisional of U.S. application Ser. No.15/714,845, which was filed on Sep. 25, 2017 and claims the benefit ofU.S. Provisional Application No. 62/400,605, by Stanslaski et al.,entitled, “ADAPTIVE DEEP BRAIN STIMULATION USING HOMEOSTATIC WINDOW,”which was filed on Sep. 27, 2016, the entire content of each of which isincorporated herein by reference.

TECHNICAL FIELD

This disclosure generally relates to electrical stimulation therapy.

BACKGROUND

Medical devices may be external or implanted, and may be used to deliverelectrical stimulation therapy to various tissue sites of a patient totreat a variety of symptoms or conditions such as chronic pain, tremor,Parkinson's disease, other movement disorders, epilepsy, urinary orfecal incontinence, sexual dysfunction, obesity, or gastroparesis. Amedical device may deliver electrical stimulation therapy via one ormore leads that include electrodes located proximate to target locationsassociated with the brain, the spinal cord, pelvic nerves, peripheralnerves, or the gastrointestinal tract of a patient. Hence, electricalstimulation may be used in different therapeutic applications, such asdeep brain stimulation (DBS), spinal cord stimulation (SCS), pelvicstimulation, gastric stimulation, or peripheral nerve field stimulation(PNFS).

A clinician may select values for a number of programmable parameters inorder to define the electrical stimulation therapy to be delivered bythe implantable stimulator to a patient. For example, the clinician mayselect one or more electrodes for delivery of the stimulation, apolarity of each selected electrode, a voltage or current amplitude, apulse width, and a pulse frequency as stimulation parameters. A set ofparameters, such as a set including electrode combination, electrodepolarity, amplitude, pulse width and pulse rate, may be referred to as aprogram in the sense that they define the electrical stimulation therapyto be delivered to the patient.

SUMMARY

In general, the disclosure describes example medical devices, systems,and techniques for defining a therapeutic window which definesboundaries for one or more parameters of electrical stimulation therapydelivered to a patient. The disclosure further describes techniques forsensing a signal of a patient and defining, based on the sensed signal,a homeostatic window. As described herein, the homeostatic window isused to control adjustment of the one or more parameters of theelectrical stimulation to the patient. The disclosure further describestechniques for selecting a signal for use in defining the homeostaticwindow as described above by determining a response of the signal to atleast one of the electrical stimulation therapy or a movement of thepatient.

In one example, the techniques of the disclosure describe a method fordelivering electrical stimulation therapy to a patient, the methodcomprising: delivering electrical stimulation therapy to tissue of apatient via electrodes; and adjusting a level of at least one parameterof the electrical stimulation therapy such that a sensed signal of thepatient is not less than a lower bound and not greater than an upperbound of a range; wherein a first bound of the upper bound and the lowerbound is one of: a magnitude of the sensed signal while receiving afirst level of the electrical stimulation therapy that is a minimumlevel sufficient to reduce one or more symptoms of a disease and whilethe patient is receiving medication for reduction of one or moresymptoms of the disease or disorder; or a magnitude of the sensed signalwhile receiving a second level of the electrical stimulation therapysufficient to cause maximum reduction of the one or more symptoms of thedisease or disorder without inducing substantial side effects in thepatient and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease; and wherein asecond bound of the upper bound and the lower bound is determined to beone of: a magnitude of the sensed signal while receiving a third levelof the third electrical stimulation therapy that is a minimum levelsufficient to reduce the one or more symptoms of the disease and whilethe patient is not receiving the medication for reduction of the atleast some of the one or more symptoms of the disease; or a magnitude ofthe sensed signal while receiving a fourth level of the electricalstimulation therapy, while the patient is not receiving the medicationfor reduction of the one or more symptoms of the disease, that issufficient to reduce the one or more symptoms of the disease or disorderbut which above the level, substantially no further substantialreduction in the one or more symptoms is achieved.

In another example, the techniques of the disclosure describe animplantable medical device (IMD) comprising: stimulation generationcircuitry configured to deliver electrical stimulation therapy to tissueof a patient via electrodes; and processing circuitry configured toadjust a level of at least one parameter of the electrical stimulationtherapy such that a sensed signal of the patient is not less than alower bound and not greater than an upper bound of a range; wherein afirst bound of the upper bound and the lower bound is one of: amagnitude of the sensed signal while receiving a first level of theelectrical stimulation therapy that is a minimum level sufficient toreduce one or more symptoms of a disease and while the patient isreceiving medication for reduction of one or more symptoms of thedisease or disorder; or a magnitude of the sensed signal while receivinga second level of the electrical stimulation therapy sufficient to causemaximum reduction of the one or more symptoms of the disease or disorderwithout inducing substantial side effects in the patient and while thepatient is not receiving the medication for reduction of the one or moresymptoms of the disease; and wherein a second bound of the upper boundand the lower bound is determined to be one of: a magnitude of thesensed signal while receiving a third level of the third electricalstimulation therapy that is a minimum level sufficient to reduce the oneor more symptoms of the disease and while the patient is not receivingthe medication for reduction of the at least some of the one or moresymptoms of the disease; or a magnitude of the sensed signal whilereceiving a fourth level of the electrical stimulation therapy, whilethe patient is not receiving the medication for reduction of the one ormore symptoms of the disease, that is sufficient to reduce the one ormore symptoms of the disease or disorder but which above the level,substantially no further substantial reduction in the one or moresymptoms is achieved.

In another example, the techniques of the disclosure describe a medicaldevice system comprising: one or more sensors; an implantable medicaldevice (IMD) comprising stimulation generation circuitry configured todeliver electrical stimulation therapy to tissue of a patient viaelectrodes; and processing circuitry configured to adjust a level of atleast one parameter of the electrical stimulation therapy such that asensed signal of the patient is not less than a lower bound and notgreater than an upper bound of a range; wherein a first bound of theupper bound and the lower bound is one of: a magnitude of the sensedsignal while receiving a first level of the electrical stimulationtherapy that is a minimum level sufficient to reduce one or moresymptoms of a disease and while the patient is receiving medication forreduction of one or more symptoms of the disease or disorder; or amagnitude of the sensed signal while receiving a second level of theelectrical stimulation therapy sufficient to cause maximum reduction ofthe one or more symptoms of the disease or disorder without inducingsubstantial side effects in the patient and while the patient is notreceiving the medication for reduction of the one or more symptoms ofthe disease; and wherein a second bound of the upper bound and the lowerbound is determined to be one of: a magnitude of the sensed signal whilereceiving a third level of the third electrical stimulation therapy thatis a minimum level sufficient to reduce the one or more symptoms of thedisease and while the patient is not receiving the medication forreduction of the at least some of the one or more symptoms of thedisease; or a magnitude of the sensed signal while receiving a fourthlevel of the electrical stimulation therapy, while the patient is notreceiving the medication for reduction of the one or more symptoms ofthe disease, that is sufficient to reduce the one or more symptoms ofthe disease or disorder but which above the level, substantially nofurther substantial reduction in the one or more symptoms is achieved.

The details of one or more examples of the techniques of this disclosureare set forth in the accompanying drawings and the description below.Other features, objects, and advantages of the techniques will beapparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a conceptual diagram illustrating an example system thatincludes an implantable medical device (IMD) configured to deliveradaptive DBS to a patient according to an example of the techniques ofthe disclosure.

FIG. 2 is a block diagram of the example IMD of FIG. 1 for deliveringadaptive DBS therapy according to an example of the techniques of thedisclosure.

FIG. 3 is a block diagram of the external programmer of FIG. 1 forcontrolling delivery of adaptive DBS therapy according to an example ofthe techniques of the disclosure.

FIG. 4 is a timing diagram illustrating the example system of FIG. 1setting a lower bound and an upper bound of a homeostatic window for aproportional signal with respect to a therapeutic window, in accordancewith an example of the techniques of the disclosure.

FIG. 5 is a graph illustrating an example operation for setting a lowerbound of the homeostatic window according to an example of thetechniques of the disclosure.

FIG. 6 is a timing diagram illustrating the example system of FIG. 1setting a lower bound and an upper bound of the homeostatic window foran inversely proportional signal according to an example of thetechniques of the disclosure.

FIG. 7 is a flowchart illustrating an example operation for setting alower bound of the homeostatic window for a proportional signalaccording to an example of the techniques of the disclosure.

FIG. 8 is a flowchart illustrating an example operation for setting anupper bound of the homeostatic window for a proportional signalaccording to an example of the techniques of the disclosure.

FIG. 9 is a flowchart illustrating an example operation for setting anupper bound of the homeostatic window for an inversely proportionalsignal according to an example of the techniques of the disclosure.

FIG. 10 is a flowchart illustrating an example operation for setting alower bound of the homeostatic window for an inversely proportionalsignal according to an example of the techniques of the disclosure.

FIG. 11 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation (DBS) based on the deviation of a signalfrom the homeostatic window according to an example of the techniques ofthe disclosure.

FIG. 12 is a flowchart illustrating an example operation for adjustingthe homeostatic window in response to patient feedback according to anexample of the techniques of the disclosure.

FIG. 13 is a flowchart illustrating an example operation for adjustingthe homeostatic window in response to a signal indicative of aphysiological parameter of the patient according to an example of thetechniques of the disclosure.

FIG. 14 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation according to an example of thetechniques of the disclosure.

FIG. 15 is a graph illustrating an example response of a signal of abrain of the patient to electrical stimulation in accordance with anexample of the techniques of the disclosure.

FIG. 16 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation according to an example of thetechniques of the disclosure.

FIG. 17 is a graph illustrating measured neurological signal of a brain120 of a patient during movement by the patient.

FIG. 18 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation according to an example of thetechniques of the disclosure.

DETAILED DESCRIPTION

A patient may suffer from one or more symptoms treatable by electricalstimulation therapy. However, the severity of these symptoms mayincrease or decrease, for example, depending on various conditions suchas the posture of the patient, the current activity of the patient(e.g., whether the patient is sleeping, exercising, working, or thelike), the stress level of the patient, drug therapy or other therapyadministered to the patient, and many other factors. Thus, a system thatdelivers electrical stimulation therapy at a constant magnitude may, insome circumstances, not deliver therapy that is sufficient to treat thesymptoms of the patient over a range of conditions. Furthermore, inother circumstances, a constant-magnitude therapy delivery system maydeliver a higher magnitude of electrical stimulation than is required totreat the symptoms of the patient, which may cause side effects in thepatient and/or cause excessive power consumption by an implantablemedical device (IMD).

Accordingly, in one example, a system including an IMD deliverselectrical stimulation therapy having one or more parameters that may beselected and adjustable based on a homeostatic window defining lower andupper bounds for a sensed signal of the patient. In some examples, thesensed signal is a neurological signal of a patient, such as aneurological signal within the Beta frequency band or Gamma frequencyband of the brain of the patient. In other examples, the sensed signalis representative of a physiological parameter of the patient sensed byone or more sensors of the system. In further examples, the systemincludes a therapeutic window that defines lower and upper bounds forone or more parameters of electrical stimulation delivered to thepatient. While maintaining the one or more parameters of the electricalstimulation within the therapeutic window, the system may increase ordecrease a magnitude of the one or more parameters of the electricalstimulation in response to changes in the sensed signal so as tomaintain the sensed signal within the bounds of the homeostatic window.In this fashion, the system may use the sensed signal and thehomeostatic window to control the magnitude of the one or moreparameters of the electrical stimulation.

For example, while a patient is not taking medication selected to reduceone or more symptoms, a clinician determines a minimum magnitude of oneor more parameters defining the electrical stimulation therapy, such asa minimum voltage amplitude or minimum current amplitude, sufficient toreduce the one or more symptoms. The clinician defines the upper boundof the homeostatic window as a magnitude of the sensed signal of thepatient at this magnitude of the electrical stimulation therapy.Further, the clinician may determine a minimum magnitude of one or moreparameters defining the electrical stimulation therapy, such as aminimum voltage amplitude or minimum current amplitude, sufficient toreduce or maintain reduction of one or more symptoms when the patient istaking medication selected to reduce the symptoms. The clinician definesa lower bound of the homeostatic window as the magnitude of the sensedsignal of the patient at this magnitude of stimulation.

In an alternate example for setting the lower bound, while the patientis off medication, the clinician delivers electrical stimulation havingone or more parameters that have a maximum magnitude (i.e., the upperbound of a therapeutic window, as described below), e.g., a maximumvoltage amplitude or maximum current amplitude defined by a therapeuticwindow. In some examples, the clinician delivers electrical stimulationhaving a value for the one or more parameters slightly below themagnitude which induces side effects in the patient. Typically,delivering electrical stimulation at a magnitude slightly less than thatwhich induces side effects causes maximal reduction of the one or moresymptoms of the disease of the patient, and therefore maximal reductionof the signal. The clinician defines a lower bound of the homeostaticwindow as the signal of the patient at this magnitude of stimulationthat is slightly less than that which induces side effects.

In a further example, the lower and upper bounds of the homeostaticwindow may be adjusted in response to patient input and/or one or morepatient conditions. However, the values of one or more parametersdefining the electrical stimulation therapy may be controlled to remainwithin a parameter range defined by lower and upper bounds of atherapeutic window. In one example, a patient may adjust one or morebounds of the homeostatic window to adjust delivery of electricalstimulation within a parameter range defined by the lower and upperbounds of the therapeutic window. In some examples, a patient mayprovide feedback to adjust one or both bounds of the homeostatic window.

In another example, the IMD may automatically adjust one or moreparameters of the electrical stimulation within a parameter rangedefined by the lower and upper bounds of the therapeutic window, e.g.,in response to the signal rising above an upper magnitude of thehomeostatic window or falling below a lower magnitude of the homeostaticwindow. In further examples, the IMD may adjust one or both bounds ofthe homeostatic window based on the sensed signal. In this example, thesystem, via the IMD, delivers electrical stimulation to the patient, andmay adjust one or more parameters defining the electrical stimulationwithin a parameter range defined by the lower and upper bounds of thetherapeutic window based on the activity of the sensed signal within thehomeostatic window. In some examples, the one or more parameters may beadjusted in a manner proportional to the magnitude of the sensed signal,e.g., directly proportional or inversely proportional.

The techniques of the disclosure may provide one or more advantages overother techniques that merely use a neurological signal, such a signalwithin a Beta frequency band of the brain of the patient, as a thresholdin that the techniques of the disclosure may allow the signal of thepatient to be maintained within a homeostatic window. This may helpprevent the system from using excessive processing and reduce currentdrain in the system by preventing the system from continuously rampingup and down the magnitude of electrical stimulation, or fromcontinuously oscillating the parameters of the electrical stimulation.Thus, such a system may allow for reduced power consumption and enhancedbattery life. Further, in some examples, a system according to thetechniques of the disclosure may reduce side effects experienced by apatient by allowing the system to remain at constant magnitudes ofelectrical stimulation for longer periods of time while the sensedsignal is maintained within the homeostatic window. Furthermore, in someexamples, a system of the present disclosure may not only delivertherapy targeted to a specific patient, but also permit adjustment ofthe therapy such that the therapy is tailored to a range of conditionsrelating to the behavior and activity of the patient. Thus, a system asdescribed in this disclosure may provide adaptive therapy that is bettersuited to the changing needs and activity magnitudes of the patient thanother methods of adaptive DB S.

Furthermore, in examples where the bounds of the homeostatic window aredefined by a neurological signal of the brain of the patient, thecorrelation of the homeostatic window to the severity of symptoms in thepatient may depend on which neurological signal is selected for use. Forexample, within a single frequency band of the neurological signal, apatient may demonstrate multiple peaks of responsiveness to electricalstimulation, each peak located at a different sub-band of the frequencyband. Further, each of these sub-bands may respond differently to theelectrical stimulation. For example, electrical stimulation may cause afirst peak magnitude at a first sub-band to substantially diminish,while the same electrical stimulation may cause a second peak magnitudeat a second sub-band to decrease only slightly. Additionally, movementof a patient may cause the neurological signal to desynchronize (e.g.,diminish in magnitude in the presence of the movement). For example,movement by the patient may cause a first peak magnitude at a firstsub-band to substantially diminish, i.e., decrease in magnitudesubstantially, while the same movement may cause a second peak magnitudeat a second sub-band to decrease only slightly relative to the decreasein the first peak magnitude in the first sub-band.

In accordance with the techniques of the disclosure, techniques aredisclosed for selecting a sub-band of the frequency band for use as acontrol signal for controlling one or more parameters defining theelectrical stimulation or to define the bounds of the homeostaticwindow. In one example, a signal in a selected sub-band is selected foruse as a control signal for controlling one or more parameters definingthe electrical stimulation or to define the bounds of the homeostaticwindow by determining the sub-band that demonstrates the least responseto electrical stimulation. In another example, a sub-band is selectedfor use as a control signal for controlling one or more parametersdefining the electrical stimulation or to define the bounds of thehomeostatic window by determining one of a plurality of sub-bands thatdemonstrates the least desynchronization response to movement by thepatient, relative to one or more other sub-bands.

FIG. 1 is a conceptual diagram illustrating an example system 100 thatincludes an implantable medical device (IMD) 106 configured to deliveradaptive deep brain stimulation to a patient 112. DBS may be adaptive inthe sense that IMD 106 may adjust, increase, or decrease the magnitudeof one or more parameters of the DB S in response to changes in patientactivity or movement, a severity of one or more symptoms of a disease ofthe patient, a presence of one or more side effects due to the DBS, orone or more sensed signals of the patient, etc. For example, one or moresensed signals of the patient may be used as a control signal such thatthe IMD 106 correlates the magnitude of the one or more parameters ofthe electrical stimulation to the magnitude of the one or more sensedsignals. According to the techniques of the disclosure, system 100, viaIMD 106, delivers electrical stimulation therapy having one or moreparameters, such as voltage or current amplitude, adjusted in responseto a signal deviating from a range defined by a homeostatic window. Inone example, an upper bound of the homeostatic window is defined as themagnitude of the signal when electrical stimulation therapy, via IMD106, is delivered to the brain 120 of patient 112 at a magnitude of oneor more parameters defining the electrical stimulation therapy, such asa voltage or current amplitude, at which further increase to themagnitude of one or more parameters defining the electrical stimulationtherapy does not cause a further reduction in the severity of thesymptoms, when the patient is not taking medication selected to reducethe symptoms (as described in more detail below). Further, the lowerbound of the homeostatic window is defined as the magnitude of thesignal when electrical stimulation therapy, via IMD 106, is delivered tothe brain 120 of patient 112 at a minimum magnitude of one or moreparameters defining the electrical stimulation therapy, such as aminimum voltage or current amplitude, that is sufficient to reduce ormaintain reduction of one or more symptoms while the patient is takingmedication selected to reduce the symptoms (as described in more detailbelow). In some examples, the signal is a neurological signal, such as asignal within a Beta frequency band of the brain 120 of patient 112 oranother signal that is considered a proportional signal, meaning thatthe signal increases as stimulation increases and decreases asstimulation decreases. In other examples, the signal may be an inverselyproportional signal, meaning that the signal decreases as stimulationincreases and increase as stimulation decreases, such as a signal withina Gamma frequency band of the brain 120 of patient 112. However, thetechniques of the disclosure provide for other physiological orneurological signals to be used to define the homeostatic window fordelivering therapy.

In yet further examples, the system delivers electrical stimulationtherapy having the one or more parameters, such as voltage or currentamplitude, adjusted in response to multiple signals, each signaldeviating from a range defined by a respective homeostatic window. Forexample, the system may sense a first neurological signal, such as asignal within a Beta frequency band of the brain 120 of patient 112within a first respective homeostatic window and a second neurologicalsignal, such as a signal within a Gamma frequency band of the brain 120of patient 112 within a second respective homeostatic window. In oneexample system, IMD 16 dynamically selects one of the first signal orthe second signal for controlling adjustment of the one or moreparameters based on a determination of which of the first signal orsecond signal most accurately corresponds to the severity of one or moresymptoms of the patient. In another example system, IMD 106 adjusts theone or more parameters based on a ratio of the first signal to thesecond signal.

In some examples, the medication taken by patient 112 is a medicationfor controlling one or more symptoms of Parkinson's disease, such astremor or rigidity due to Parkinson's disease. Such medications includeextended release forms of dopamine agonists, regular forms of dopamineagonists, controlled release forms of carbidopa/levodopa (CD/LD),regular forms of CD/LD, entacapone, rasagiline, selegiline, andamantadine. Typically, to set the upper bound of the homeostatic window,the patient has been off medication, i.e., the upper bound is set whenthe patient is not taking medication selected to reduce the symptoms.The patient may be considered to be not taking the medication when thepatient, prior to the time the upper bound is set, has not taken themedication for at least approximately 72 hours for extended releaseforms of dopamine agonists, the patient has not taken the medication forat least approximately 24 hours for regular forms of dopamine agonistsand controlled release forms of CD/LD, and the patient has not taken themedication for at least approximately 12 hours for regular forms ofCD/LD, entacapone, rasagiline, selegiline, and amantadine. Further,typically, to set the lower bound of the homeostatic window, at the timethe lower bound is set, the patient has been on medication, e.g., takenthe medication at prescribed dosages and intervals, for at leastapproximately 72 hours for extended release forms of dopamine agonists,the patient has been on medication, e.g., taken the medication atprescribed dosages and intervals, for at least approximately 24 hoursfor regular forms of dopamine agonists and controlled release forms ofCD/LD, and the patient has been on medication, e.g., taken themedication at prescribed dosages and intervals, for at leastapproximately 12 hours for regular forms of CD/LD, entacapone,rasagiline, selegiline, and amantadine.

As described herein, “reducing” or “suppressing” the symptoms of thepatient refer to alleviating, in whole or in part, the severity of oneor more symptoms of the patient. In one example, a clinician makes adetermination of the severity of one or more symptoms of Parkinson'sdisease of patient 112 with reference to the Unified Parkinson's DiseaseRating Scale (UPDRS) or the Movement Disorder Society-Sponsored Revisionof the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Adiscussion of the application of the MDS-UPDRS is provided by MovementDisorder Society-Sponsored Revision of the Unified Parkinson's DiseaseRating Scale (MDS-UPDRS): Scale Presentation and Clinimetric TestingResults, C. Goetz et al, Movement Disorders, Vol. 23, No. 15, pp.2129-2170 (2008), the content of which is incorporated herein in itsentirety.

As described above, a clinician determines the upper bound of thehomeostatic window while the patient is not taking medication, andwhile, via IMD 106, electrical stimulation therapy is delivered to thebrain 120 of patient 112. In one example, a clinician determines thepoint at which increasing the magnitude of one or more parametersdefining the electrical stimulation therapy, such as voltage amplitudeor current amplitude, does not provide further reduction or suppressionof one or more symptoms of the patient 112. For example, the clinicianmay gradually increase the magnitude of one or more parameters definingthe electrical stimulation therapy and determine the point at whichfurther increase to the magnitude of one or more parameters defining theelectrical stimulation therapy does not cause a further reduction in theseverity of the symptoms of Parkinson's disease, such as rigidity, inpatient 112, as measured by a further reduction in the score of patient112 under the UPDRS or MDS-UPDRS.

In another example, the clinician measures a physiological parameter ofpatient 112 related to one or more symptoms of the disease of patient112 and determines the point at which further increase to the magnitudeof one or more parameters defining the electrical stimulation therapydoes not cause a further positive effect in the reduction of the one ormore symptoms of the disease of patient 112. For example, the clinicianmay measure a wrist flexion of patient 112, which correlates to rigidityin patient 112, and determines the point at which further increase tothe magnitude of one or more parameters defining the electricalstimulation therapy does not cause a further positive effect in thewrist flexion of patient 112. Other examples of physiological parametersmay include signals from an accelerometer indicative of a tremor ofpatient 112. At this magnitude of the one or more parameters definingthe electrical stimulation therapy, at which further increase inmagnitude does not cause further reduction in severity of symptoms, theclinician measures the magnitude of the signal of the patient 112 andsets this magnitude as the upper bound of the homeostatic window. Insome examples, the clinician may select an upper bound of thehomeostatic window to be a predetermined amount, e.g., 5% or 10%, lowerthan the magnitude at which the symptoms of the patient 112 receive nofurther reduction in response to increased magnitude of one or moreparameters defining the electrical stimulation therapy. In someexamples, setting the upper bound to be lower than the measuredmagnitude may serve to select therapy parameter magnitude that prevents,during subsequent use, discomfort to patient 112 due to side effects ofthe therapy, and/or unnecessary consumption of power resources.

As also described above, a clinician determines the lower bound of thehomeostatic window while the patient is taking medication, and while,via IMD 106, electrical stimulation therapy is delivered to the brain120 of patient 112. In one example, a clinician determines the point atwhich decreasing the magnitude of one or more parameters defining theelectrical stimulation therapy causes break-through of one or moresymptoms of the patient 112. This break-through of symptoms may refer tore-emergence of at least some symptoms that were substantiallysuppressed up to the point of re-emergence due to the decrease inmagnitude of the one or more electrical stimulation therapy parameters.For example, the clinician may gradually decrease the magnitude of oneor more parameters defining the electrical stimulation therapy anddetermine the point at which the symptoms of Parkinson's disease inpatient 112 emerge, as measured by sudden increase with respect totremor or rigidity, in the score of patient 112 under the UPDRS orMDS-UPDRS. In another example, the clinician measures a physiologicalparameter of patient 112 correlated to one or more symptoms of thedisease of patient 112 (e.g., wrist flexion of patient 112) anddetermines the point at which further decrease to the magnitude of oneor more parameters defining the electrical stimulation therapy causes asudden increase in the one or more symptoms of the disease of patient112 (e.g., onset of lack of wrist flexion of patient 112).

At the magnitude of one or more parameters defining the electricalstimulation therapy at which further decrease to the magnitude of one ormore parameters defining the electrical stimulation therapy causes asudden increase in the one or more symptoms of the disease of patient112, the clinician measures the magnitude of the signal of the patient112 and sets this magnitude as the lower bound of the homeostaticwindow. In some examples, the clinician may select a lower bound of thehomeostatic window to be a predetermined amount, e.g., 5% or 10%, higherthan the magnitude at which the symptoms of the patient 112 first emergeduring decrease in the magnitude of one or more electrical stimulationparameters to prevent emergence of the symptoms of the patient 112during subsequent use.

In another example, the clinician sets the lower bound by first ensuringthat the patient is off medication for the one or more symptoms. In thisexample, the clinician delivers electrical stimulation having a valuefor the one or more parameters approximately equal to the upper bound ofthe therapeutic window. In some examples, the clinician deliverselectrical stimulation having a value for the one or more parametersslightly below the magnitude which induces side effects in the patient112. Typically, this causes maximal reduction of the one or moresymptoms of the disease of the patient 112, and therefore maximalreduction of the signal. At this magnitude of the one or moreparameters, the clinician measures the magnitude of the signal of thepatient 112 and sets, via external programmer 104, this magnitude as thelower bound of the homeostatic window. In some examples, the clinicianmay select a value for the lower bound of the homeostatic window to be apredetermined amount, e.g., 5% or 10%, lower than the magnitude at whichthe symptoms of the patient 112 emerge to prevent emergence of thesymptoms of the patient 112 during subsequent use.

In still further examples, the clinician sets the upper bound and thelower bound as a ratio of one another. For example, the clinician mayset a value for the upper bound as described above, and set a value forthe lower bound as a percentage or proportion of the upper bound. Inanother example, the clinician may set a value for the lower bound asdescribed above, and set a value for the upper bound as a percentage orproportion of the lower bound. In yet a further example, the cliniciansets at least one of the upper bound at a maximum amplitude of thesignal of patient 112 during phase amplitude coupling and the lowerbound at a minimum amplitude of the signal of patient 112 during phaseamplitude coupling.

In the aforementioned manner, upper and lower bounds may be set for aproportional signal. A signal is considered a proportional signal if achange in the signal magnitude will trigger system 100 to make acorresponding change in the therapy delivered by the system. An exampleproportional signal includes a neurological signal such as a signalwithin a Beta frequency band of brain 120 of patient 112. The Betafrequency band is about 13 Hertz to about 30 Hertz. For instance, system100 may be configured such that, in response to sensing a decrease insignal magnitude for a proportional signal, a magnitude of therapy(e.g., stimulation voltage or current amplitude) may be decreased bysystem 100. Conversely, system 100 may be configured such that, inresponse to sensing an increase in signal magnitude, a magnitude oftherapy may be increased by system 100. Other signals, includingneurological signals such as a signal within the Gamma frequency band ofbrain 120 of patient 112, are inversely proportional signals. The Gammafrequency band is about 35 Hertz to about 200 Hertz. A high magnitude ofsuch inversely proportional signals may correlate to the presence ofside effects, such as dyskinesia. For these inversely proportionalsignals, system 100 may be configured such that, in response to sensingan increase in the sensed signal magnitude, IMD 106 may decrease amagnitude of one or more parameters of the electrical stimulationtherapy, and in response to sensing a decrease in the sensed signalmagnitude, IMD 106 may increase the magnitude of one or more parametersof the electrical stimulation therapy. As described herein, themagnitude of a sensed neurological signal, such as a signal within aBeta or Gamma frequency range, refers to a spectral power of theneurological signal.

For signals such as neurological signals within the Gamma frequency bandthat are inversely proportional, the setting of upper and lower boundsof a homeostatic window is accomplished in a manner similar to the wayin which the lower and upper bounds, respectively, of a homeostaticwindow are set for proportional signals. This is discussed furtherbelow.

According to the techniques of the disclosure, the therapeutic windowdefines a parameter range for one or more parameters defining theelectrical stimulation. A clinician may set an upper bound for thetherapeutic window as a maximum value of one or more parameters definingthe electrical stimulation. In an example of a voltage-controlledsystem, the clinician sets the upper bound of the therapeutic window asa maximum voltage amplitude of the electrical stimulation that thesystem may not exceed. In an example of a current-controlled system, theclinician sets the upper bound of the therapeutic window as a maximumcurrent amplitude of the electrical stimulation that the system may notexceed. Typically, the upper bound of the therapeutic window is amaximum safe magnitude of the stimulation. In other words, the upperbound of the therapeutic window is a magnitude substantially below apain threshold or a tissue injury threshold of the patient. However, insome cases, the upper bound of the therapeutic window is the highestmagnitude of the stimulation that does not cause discomfort to thepatient.

A clinician may set a lower bound for the therapeutic window as aminimum of one or more parameters defining the electrical stimulation.In one example, a clinician sets the lower bound for the therapeuticwindow as a minimum threshold magnitude of electrical stimulation thatthe system should continuously provide to the patient for effectivetherapy to substantially suppress symptoms. In an example of avoltage-controlled system, the clinician sets the lower bound of thetherapeutic window as a minimum voltage amplitude of the electricalstimulation that the system should continuously provide to the patientto suppress symptoms. In an example of a current-controlled system, theclinician sets the lower bound of the therapeutic window as a minimumcurrent amplitude of the electrical stimulation that the system shouldcontinuously provide to the patient for therapy to suppress symptoms.

Additionally, in one example of the techniques of the disclosure, thesystem monitors a signal of the patient. In one example, the signal is aneurological signal of a patient, such as a signal within a Betafrequency band or a Gamma frequency band of the brain of the patient. Inanother example, the signal is a transformation of a neurological signalof a patient that correlates to a probability that the patient willexperience an event, such as a seizure or fall. In yet a furtherexample, the signal is a signal indicative of a physiological parameterof the patient, such as a severity of a symptom of the patient, aposture of the patient, a respiratory function of the patient, or anactivity level of the patient.

The system, via the IMD, delivers electrical stimulation to the patient,wherein one or more parameters defining the electrical stimulation areproportional to the magnitude of the monitored signal.

As an example wherein the signal is a signal within a Beta frequencyband of brain 120 of patient 112, system 100 monitors the Beta bandsignal magnitude of patient 112. Upon detecting that the beta magnitudeof patient 112 exceeds the upper bound of the homeostatic window, thesystem increases stimulation, e.g., increases stimulation voltage orcurrent amplitude. The stimulation may be increased at a maximum ramprate determined by the clinician, until the beta magnitude returns to amagnitude within the homeostatic window, or until the magnitude of theelectrical stimulation reaches an upper limit of a therapeutic windowdetermined by the clinician. Upon detecting that the beta magnitude ofpatient 112 falls below the lower bound of the homeostatic window, thesystem decreases stimulation, e.g., decreases stimulation voltage orcurrent amplitude. The stimulation may be decreased at a maximum ramprate determined by the clinician, until the beta magnitude returns to amagnitude within the homeostatic window, or until the magnitude of theelectrical stimulation reaches a lower limit of a therapeutic windowdetermined by the clinician. Upon detecting that the beta magnitude hasreturned to within the bounds of the homeostatic window, the system mayhold the magnitude of the electrical stimulation constant. In thismanner, while maintaining the one or more parameters of the electricalstimulation within the therapeutic window, the system may increase ordecrease a magnitude of the one or more parameters of the electricalstimulation in response to changes in the sensed signal so as tomaintain the sensed signal within the bounds of the homeostatic window.In this fashion, the system may use the sensed signal and thehomeostatic window to control the magnitude of the one or moreparameters of the electrical stimulation. Additional exampleimplementations of the homeostatic window are provided in further detailbelow.

In some examples, the maximum ramp rate is a parameter set by theclinician. For example, a clinician may determine the tolerance of apatient 112 to a change in magnitude of the electrical stimulation overa period of time and set the maximum ramp rate to accommodate thecomfort of patient 112. Further, as the rate of change of one or moreparameters of electrical stimulation increases, some systems may loseresolution in the ability to detect control signals, such as the signalof patient 112. Thus, in some examples, the clinician may set themaximum ramp rate as a maximum ramp rate achievable by system 100 whilestill reliability detecting one or more neurological signals of patient112. In some examples, the maximum ramp rate is at least approximately0.1 Volts per 400 milliseconds. In some examples, the clinician titratesa plurality of ramps, such as 0.1 Volts per 400 milliseconds; 0.5 Voltsper 400 milliseconds; 1 Volt per 400 milliseconds; and 2 Volts per 400milliseconds, and selects a maximum ramp rate based on the tolerance ofthe patient and the reliability of the system 100.

System 100 may be configured to treat a patient condition, such as amovement disorder, neurodegenerative impairment, a mood disorder, or aseizure disorder of patient 112. Patient 112 ordinarily is a humanpatient. In some cases, however, therapy system 100 may be applied toother mammalian or non-mammalian, non-human patients. While movementdisorders and neurodegenerative impairment are primarily referred toherein, in other examples, therapy system 100 may provide therapy tomanage symptoms of other patient conditions, such as, but not limitedto, seizure disorders (e.g., epilepsy) or mood (or psychological)disorders (e.g., major depressive disorder (MDD), bipolar disorder,anxiety disorders, post-traumatic stress disorder, dysthymic disorder,and obsessive-compulsive disorder (OCD)). At least some of thesedisorders may be manifested in one or more patient movement behaviors.As described herein, a movement disorder or other neurodegenerativeimpairment may include symptoms such as, for example, muscle controlimpairment, motion impairment or other movement problems, such asrigidity, spasticity, bradykinesia, rhythmic hyperkinesia, nonrhythmichyperkinesia, and akinesia. In some cases, the movement disorder may bea symptom of Parkinson's disease. However, the movement disorder may beattributable to other patient conditions.

Example therapy system 100 includes medical device programmer 104,implantable medical device (IMD) 106, lead extension 110, and leads 114Aand 114B with respective sets of electrodes 116, 118. In the exampleshown in FIG. 1 , electrodes 116, 118 of leads 114A, 114B are positionedto deliver electrical stimulation to a tissue site within brain 120,such as a deep brain site under the dura mater of brain 120 of patient112. In some examples, delivery of stimulation to one or more regions ofbrain 120, such as the subthalamic nucleus, globus pallidus or thalamus,may be an effective treatment to manage movement disorders, such asParkinson's disease. Some or all of electrodes 116, 118 also may bepositioned to sense neurological brain signals within brain 120 ofpatient 112. In some examples, some of electrodes 116, 118 may beconfigured to sense neurological brain signals and others of electrodes116, 118 may be configured to deliver adaptive electrical stimulation tobrain 120. In other examples, all of electrodes 116, 118 are configuredto both sense neurological brain signals and deliver adaptive electricalstimulation to brain 120.

IMD 106 includes a therapy module (e.g., which may include processingcircuitry, signal generation circuitry or other electrical circuitryconfigured to perform the functions attributed to IMD 106) that includesa stimulation generator configured to generate and deliver electricalstimulation therapy to patient 112 via a subset of electrodes 116, 118of leads 114A and 114B, respectively. The subset of electrodes 116, 118that are used to deliver electrical stimulation to patient 112, and, insome cases, the polarity of the subset of electrodes 116, 118, may bereferred to as a stimulation electrode combination. As described infurther detail below, the stimulation electrode combination can beselected for a particular patient 112 and target tissue site (e.g.,selected based on the patient condition). The group of electrodes 116,118 includes at least one electrode and can include a plurality ofelectrodes. In some examples, the plurality of electrodes 116 and/or 118may have a complex electrode geometry such that two or more electrodesare located at different positions around the perimeter of therespective lead.

In some examples, the neurological signals sensed within brain 120 mayreflect changes in electrical current produced by the sum of electricalpotential differences across brain tissue. Examples of neurologicalbrain signals include, but are not limited to, electrical signalsgenerated from local field potentials (LFP) sensed within one or moreregions of brain 120, such as an electroencephalogram (EEG) signal, oran electrocorticogram (ECoG) signal. Local field potentials, however,may include a broader genus of electrical signals within brain 120 ofpatient 112.

In some examples, the neurological brain signals that are used to selecta stimulation electrode combination may be sensed within the same regionof brain 120 as the target tissue site for the electrical stimulation.As previously indicated, these tissue sites may include tissue siteswithin anatomical structures such as the thalamus, subthalamic nucleusor globus pallidus of brain 120, as well as other target tissue sites.The specific target tissue sites and/or regions within brain 120 may beselected based on the patient condition. Thus, in some examples, both astimulation electrode combination and sense electrode combinations maybe selected from the same set of electrodes 116, 118. In other examples,the electrodes used for delivering electrical stimulation may bedifferent than the electrodes used for sensing neurological brainsignals.

Electrical stimulation generated by IMD 106 may be configured to managea variety of disorders and conditions. In some examples, the stimulationgenerator of IMD 106 is configured to generate and deliver electricalstimulation pulses to patient 112 via electrodes of a selectedstimulation electrode combination. However, in other examples, thestimulation generator of IMD 106 may be configured to generate anddeliver a continuous wave signal, e.g., a sine wave or triangle wave. Ineither case, a stimulation generator within IMD 106 may generate theelectrical stimulation therapy for DBS according to a therapy programthat is selected at that given time in therapy. In examples in which IMD106 delivers electrical stimulation in the form of stimulation pulses, atherapy program may include a set of therapy parameter values (e.g.,stimulation parameters), such as a stimulation electrode combination fordelivering stimulation to patient 112, pulse frequency, pulse width, anda current or voltage amplitude of the pulses. As previously indicated,the electrode combination may indicate the specific electrodes 116, 118that are selected to deliver stimulation signals to tissue of patient112 and the respective polarities of the selected electrodes.

IMD 106 may be implanted within a subcutaneous pocket above theclavicle, or, alternatively, on or within cranium 122 or at any othersuitable site within patient 112. Generally, IMD 106 is constructed of abiocompatible material that resists corrosion and degradation frombodily fluids. IMD 106 may comprise a hermetic housing to substantiallyenclose components, such as a processor, therapy module, and memory.

As shown in FIG. 1 , implanted lead extension 110 is coupled to IMD 106via connector 108 (also referred to as a connector block or a header ofIMD 106). In the example of FIG. 1 , lead extension 110 traverses fromthe implant site of IMD 106 and along the neck of patient 112 to cranium122 of patient 112 to access brain 120. In the example shown in FIG. 1 ,leads 114A and 114B (collectively “leads 114”) are implanted within theright and left hemispheres, respectively, of patient 112 in orderdeliver electrical stimulation to one or more regions of brain 120,which may be selected based on the patient condition or disordercontrolled by therapy system 100. The specific target tissue site andthe stimulation electrodes used to deliver stimulation to the targettissue site, however, may be selected, e.g., according to the identifiedpatient behaviors and/or other sensed patient parameters. Other lead 114and IMD 106 implant sites are contemplated. For example, IMD 106 may beimplanted on or within cranium 122, in some examples. Or leads 114 maybe implanted within the same hemisphere or IMD 106 may be coupled to asingle lead implanted in a single hemisphere.

Existing lead sets include axial leads carrying ring electrodes disposedat different axial positions and so-called “paddle” leads carryingplanar arrays of electrodes. Selection of electrode combinations withinan axial lead, a paddle lead, or among two or more different leadspresents a challenge to the clinician. In some examples, more complexlead array geometries may be used.

Although leads 114 are shown in FIG. 1 as being coupled to a common leadextension 110, in other examples, leads 114 may be coupled to IMD 106via separate lead extensions or directly to connector 108. Leads 114 maybe positioned to deliver electrical stimulation to one or more targettissue sites within brain 120 to manage patient symptoms associated witha movement disorder of patient 112. Leads 114 may be implanted toposition electrodes 116, 118 at desired locations of brain 120 throughrespective holes in cranium 122. Leads 114 may be placed at any locationwithin brain 120 such that electrodes 116, 118 are capable of providingelectrical stimulation to target tissue sites within brain 120 duringtreatment. For example, electrodes 116, 118 may be surgically implantedunder the dura mater of brain 120 or within the cerebral cortex of brain120 via a burr hole in cranium 122 of patient 112, and electricallycoupled to IMD 106 via one or more leads 114.

In the example shown in FIG. 1 , electrodes 116, 118 of leads 114 areshown as ring electrodes. Ring electrodes may be used in DBSapplications because they are relatively simple to program and arecapable of delivering an electrical field to any tissue adjacent toelectrodes 116, 118. In other examples, electrodes 116, 118 may havedifferent configurations. For example, in some examples, at least someof the electrodes 116, 118 of leads 114 may have a complex electrodearray geometry that is capable of producing shaped electrical fields.The complex electrode array geometry may include multiple electrodes(e.g., partial ring or segmented electrodes) around the outer perimeterof each lead 114, rather than one ring electrode. In this manner,electrical stimulation may be directed in a specific direction fromleads 114 to enhance therapy efficacy and reduce possible adverse sideeffects from stimulating a large volume of tissue. In some examples, ahousing of IMD 106 may include one or more stimulation and/or sensingelectrodes. In alternative examples, leads 114 may have shapes otherthan elongated cylinders as shown in FIG. 1 . For example, leads 114 maybe paddle leads, spherical leads, bendable leads, or any other type ofshape effective in treating patient 112 and/or minimizing invasivenessof leads 114.

In the example shown in FIG. 1 , IMD 106 includes a memory to store aplurality of therapy programs that each define a set of therapyparameter values. In some examples, IMD 106 may select a therapy programfrom the memory based on various parameters, such as sensed patientparameters and the identified patient behaviors. IMD 106 may generateelectrical stimulation based on the selected therapy program to managethe patient symptoms associated with a movement disorder.

External programmer 104 wirelessly communicates with IMD 106 as neededto provide or retrieve therapy information. Programmer 104 is anexternal computing device that the user, e.g., a clinician and/orpatient 112, may use to communicate with IMD 106. For example,programmer 104 may be a clinician programmer that the clinician uses tocommunicate with IMD 106 and program one or more therapy programs forIMD 106. Alternatively, programmer 104 may be a patient programmer thatallows patient 112 to select programs and/or view and modify therapyparameters. The clinician programmer may include more programmingfeatures than the patient programmer. In other words, more complex orsensitive tasks may only be allowed by the clinician programmer toprevent an untrained patient from making undesirable changes to IMD 106.

When programmer 104 is configured for use by the clinician, programmer104 may be used to transmit initial programming information to IMD 106.This initial information may include hardware information, such as thetype of leads 114 and the electrode arrangement, the position of leads114 within brain 120, the configuration of electrode array 116, 118,initial programs defining therapy parameter values, and any otherinformation the clinician desires to program into IMD 106. Programmer104 may also be capable of completing functional tests (e.g., measuringthe impedance of electrodes 116, 118 of leads 114).

The clinician may also store therapy programs within IMD 106 with theaid of programmer 104. During a programming session, the clinician maydetermine one or more therapy programs that may provide efficacioustherapy to patient 112 to address symptoms associated with the patientcondition, and, in some cases, specific to one or more different patientstates, such as a sleep state, movement state or rest state. Forexample, the clinician may select one or more stimulation electrodecombination with which stimulation is delivered to brain 120. During theprogramming session, the clinician may evaluate the efficacy of thespecific program being evaluated based on feedback provided by patient112 or based on one or more physiological parameters of patient 112(e.g., muscle activity, muscle tone, rigidity, tremor, etc.).Alternatively, identified patient behavior from video information may beused as feedback during the initial and subsequent programming sessions.Programmer 104 may assist the clinician in the creation/identificationof therapy programs by providing a methodical system for identifyingpotentially beneficial therapy parameter values.

Programmer 104 may also be configured for use by patient 112. Whenconfigured as a patient programmer, programmer 104 may have limitedfunctionality (compared to a clinician programmer) in order to preventpatient 112 from altering critical functions of IMD 106 or applicationsthat may be detrimental to patient 112. In this manner, programmer 104may only allow patient 112 to adjust values for certain therapyparameters or set an available range of values for a particular therapyparameter.

Programmer 104 may also provide an indication to patient 112 whentherapy is being delivered, when patient input has triggered a change intherapy or when the power source within programmer 104 or IMD 106 needsto be replaced or recharged. For example, programmer 112 may include analert LED, may flash a message to patient 112 via a programmer display,generate an audible sound or somatosensory cue to confirm patient inputwas received, e.g., to indicate a patient state or to manually modify atherapy parameter.

Therapy system 100 may be implemented to provide chronic stimulationtherapy to patient 112 over the course of several months or years.However, system 100 may also be employed on a trial basis to evaluatetherapy before committing to full implantation. If implementedtemporarily, some components of system 100 may not be implanted withinpatient 112. For example, patient 112 may be fitted with an externalmedical device, such as a trial stimulator, rather than IMD 106. Theexternal medical device may be coupled to percutaneous leads or toimplanted leads via a percutaneous extension. If the trial stimulatorindicates DBS system 100 provides effective treatment to patient 112,the clinician may implant a chronic stimulator within patient 112 forrelatively long-term treatment.

Although IMD 104 is described as delivering electrical stimulationtherapy to brain 120, IMD 106 may be configured to direct electricalstimulation to other anatomical regions of patient 112. In otherexamples, system 100 may include an implantable drug pump in additionto, or in place of, IMD 106. Further, an IMD may provide otherelectrical stimulation such as spinal cord stimulation to treat amovement disorder.

According to the techniques of the disclosure, system 100 defines ahomeostatic window and a therapeutic window for delivering adaptive DBSto patient 112. System 100 may adaptively deliver electrical stimulationand adjust one or more parameters defining the electrical stimulationwithin a parameter range defined by the lower and upper bounds of thetherapeutic window based on the activity of the sensed signal within thehomeostatic window. For example, system 100 may adjust the one or moreparameters defining the electrical stimulation in response to the sensedsignal falling below the lower bound or exceeding the upper bound of thehomeostatic window, but may not adjust the one or more parametersdefining the electrical stimulation such that they fall below the lowerbound or exceed the upper bound of the therapeutic window.

In one example, external programmer 104 issues commands to IMD 106causing IMD 106 to deliver electrical stimulation therapy via electrodes116, 118 via leads 114. As described above, the therapeutic windowdefines an upper bound and a lower bound for one or more parametersdefining the delivery of electrical stimulation therapy to patient 112.For example, the one or more parameters include a current amplitude (fora current-controlled system) or a voltage amplitude (for avoltage-controlled system), a pulse rate or frequency, and a pulsewidth. In examples where the electrical stimulation is deliveredaccording to a “burst” of pulses, or a series of electrical pulsesdefined by an “on-time” and an “off-time,” the one or more parametersmay further define one or more of a number of pulses per burst, anon-time, and an off-time. In one example, the therapeutic window definesan upper bound and a lower bound for one or more parameters, such asupper and lower bounds for a current amplitude of the electricalstimulation therapy (in current-controlled systems) or upper and lowerbounds of a voltage amplitude of the electrical stimulation therapy (involtage-controlled systems). While the examples herein are typicallygiven with respect to adjusting a voltage amplitude or a currentamplitude, the techniques herein may equally be applied to a homeostaticwindow and a therapeutic window using other parameters, such as, e.g.,pulse rate or pulse width. Example implementations of the therapeuticwindow are provided in further detail below.

Additionally, in one example of the techniques of the disclosure, system100 provides adaptive DBS. For example, system 100 may provide adaptiveDBS by permitting a patient 112, e.g., via a patient programmer 104, toindirectly adjust the activation, deactivation, and magnitude of theelectrical stimulation by adjusting the lower and upper bounds of thehomeostatic window. For example, by adjusting one or both bounds of thehomeostatic window, patient 112 may adjust the point at which the sensedsignal deviates from the homeostatic window, triggering system 100 toadjust one or more parameters of the electrical stimulation within aparameter range defined by the lower and upper bounds of the therapeuticwindow.

In some examples, a patient may provide feedback, e.g., via programmer104, to adjust one or both bounds of the homeostatic window. In anotherexample, programmer 104 and/or IMD 106 may automatically adjust one orboth bounds of the homeostatic window, as well as one or more parametersof the electrical stimulation within the parameter range defined by thelower and upper bounds of the therapeutic window. For example, IMD 106may adjust the delivery of adaptive DBS by automatically adjusting oneor more bounds of the homeostatic window, e.g., in response to aphysiological parameter sensed by one or more sensors 109 of system 100.As a further example, programmer 104 and/or IMD 106 may automaticallyadjust one or more bounds of the homeostatic window based on one or morephysiological or neurological signals of patient 112 sensed by IMD 106.For example, in response to deviations in the signal of the patientoutside of the homeostatic window, system 100 (e.g., IMD 106 orprogrammer 104) may automatically adjust one or more parameters definingthe electrical stimulation therapy delivered to the patient in a mannerthat is proportional to the magnitude of the sensed signal and withinthe therapeutic window defining lower and upper bounds for the one ormore parameters. The adjustment to the one or more stimulation therapyparameters based on the deviation of the sensed signal may beproportional or inversely proportional to the magnitude of the signal.

Hence, in some examples, system 100, via programmer 104 or IMD 106, mayadjust one or more parameters of the electrical stimulation, such asvoltage or current amplitude, within the therapeutic window based onpatient input that adjusts the homeostatic window, or based on one ormore signals, such as sensed physiological parameters or sensedneurological signals, or a combination of two or more of the above. Inparticular, system 100 may adjust a parameter of the electricalstimulation, automatically and/or in response to patient input thatadjusts the homeostatic window, provided the value of the electricalstimulation parameter is constrained to remain within a range specifiedby the upper and lower bounds of the therapeutic window. This range maybe considered to include the upper and lower bounds themselves.

In some examples where system 100 adjusts multiple parameters of theelectrical stimulation, system 100 may adjust at least one of a voltageamplitude or current amplitude, a stimulation frequency, a pulse width,or a selection of electrodes, and the like. In such an example, theclinician may set an order or sequence for adjustment of the parameters(e.g., adjust voltage amplitude or current amplitude, then adjuststimulation frequency, and then adjust the selection of electrodes). Inother examples, system 100 may randomly select a sequence of adjustmentsto the multiple parameters. In either example, system 100 may adjust avalue of a first parameter of the parameters of the electricalstimulation. If the signal does not exhibit a response to the adjustmentof the first parameter, system 100 may adjust a value of a secondparameter of the parameters of the electrical stimulation, and so onuntil the signal returns to within the homeostatic window.

Also, in some examples, system 100 may adjust the upper and/or lowerbounds of the homeostatic window based on patient input, or based on oneor more signals, such as sensed physiological parameters or sensedneurological signals, or a combination of two or more of the above. Inthis manner, system 100 may provide not only adaptive adjustment of oneor more parameters of the electrical stimulation within the rangedefined by the therapeutic window, but also, in some examples, adaptiveadjustment of the range of the homeostatic window itself, e.g.,adjustment of the thresholds that cause system 100 to adaptively adjustthe one or more parameters of the electrical stimulation, based onpatient input, one or more sensed signals, or a combination of two ormore of patient input. Hence, IMD 106 of system 100 may configured suchthat, adjustments to the upper and lower bounds of the homeostaticwindow, result in IMD 106 adjusting stimulation parameters within thetherapeutic window. As an illustration, if a sensed physiologicalparameter of sensed neurological signal exceeds the upper bound or thehomeostatic window or drops below the lower bound of the homeostaticwindow, system 100 may adjust values of one or more stimulationparameters to drive the sensed physiological parameter or sensedneurological signal back into the homeostatic window, e.g., subject tokeeping the therapy parameter value within the range prescribed by thetherapeutic window.

To adaptively adjust DBS based on a neurological signal, for example,two or more electrodes 116, 118 of IMD 106 may be configured to monitora neurological signal of patient 112. In some examples, at least one ofelectrodes 116, 118 may be provided on a housing of IMD 106, providing aunipolar stimulation and/or sensing configuration. In one example, theneurological signal is a signal within a Beta frequency band of brain120 of patient 112. For example, neurological signals within the Betafrequency band of patient 112 may correlate to one or more symptoms ofParkinson's disease in patient 112. Generally speaking, neurologicalsignals within the Beta frequency of patient 112 may be approximatelyproportional to the severity of the symptoms of patient 112. Forexample, as tremor induced by Parkinson's disease increases,neurological signals within the Beta frequency of patient 112 increase.Moreover, neurological signals within the Beta frequency are consideredproportional because system 100 may be configured such that an increasein signal magnitude may trigger system 100 to increase deliveredstimulation therapy magnitude according to disclosed techniques.Similarly, as tremor induced by Parkinson's disease decreases,neurological signals within the Beta frequency of patient 112 decrease,and the decrease may trigger system 100 to decrease the magnitude ofdelivered stimulation.

In another example, the neurological signal monitored by IMD 106 may bea signal within a gamma frequency band of brain 120 of patient 112.Neurological signals within the Gamma frequency band of patient 112 mayalso correlate to one or more side effects in patient 112 resulting fromelectrical stimulation therapy. However, in contrast to neurologicalsignals within the Beta frequency band, generally speaking, neurologicalsignals within the Gamma frequency band of patient 112 may beapproximately inversely proportional to the magnitude of stimulationmagnitude that is delivered by system 100 in response to the signal. Inother words, an elevated magnitude of the signal within the Gammafrequency band may indicate the presence of side effects, such asdyskinesia. For example, system 100 may be configured such that, as themagnitude of a signal within the Gamma frequency band increases, therapymagnitudes may be decreased by system 100 in response thereto, therebyreducing or eliminating side effects. Conversely, system 100 may beconfigured such that as the magnitude of a signal within the Gammafrequency band decreases, therapy magnitudes may be increased by system100 according to techniques disclosed herein. Accordingly, IMD 106, inresponse to variations in the monitored neurological signal, e.g., suchas real-time or near real-time variations, may deliver adaptive DBS topatient 112 by adjusting the magnitude of one or more parametersdefining the electrical stimulation therapy, such as the voltage orcurrent amplitude of electrical stimulation pulses. For example, IMD 106may reduce a magnitude of a parameter, such as a current or voltageamplitude of the electrical stimulation therapy, in response to themagnitude of a monitored neurological signal within the Beta frequencyband falling below the lower bound of the homeostatic window establishedfor the Beta band signal. In this case, by falling below the lower boundof the homeostatic window, the Beta band signal indicates that symptomsare reduced, such that stimulation parameter magnitude likewise isreduced by IMD 106. Alternatively, IMD 106 may increase a magnitude of astimulation parameter, such as a current or voltage amplitude of theelectrical stimulation therapy, in response to the magnitude of themonitored signal within the Beta frequency band exceeding the upperbound of the homeostatic window. In this case, by exceeding the upperbound of the homeostatic window, the Beta band signal indicates thatsymptoms have increased to an undesirable amount, such that stimulationparameter magnitude is increased by IMD 106, e.g., to force the Betaband signal back into the homeostatic window, and thereby suppress orpartially suppress symptoms.

Conversely, IMD 106 may be configured to increase a magnitude of astimulation therapy parameter, such as a current or voltage amplitude ofthe electrical stimulation therapy, in response to the magnitude of amonitored signal within the Gamma frequency band falling below the lowerbound of a homeostatic window established for the Gamma band signal. Inthis case, by falling below the lower bound of the homeostatic window,the Gamma band signal indicates that side effects have reduced, suchthat the stimulation parameter magnitude is increased by IMD 106.Alternatively, IMD 106 may reduce a magnitude of a stimulationparameter, such as a current or voltage amplitude of the electricalstimulation therapy, in response to the magnitude of a monitored signalwithin the Gamma frequency band rising above the upper bound of thehomeostatic window. In this case, by exceeding the upper bound of thehomeostasis window, the Gamma band signal indicates that side effectshave increased to an undesirable amount, such that stimulation parametermagnitude is reduced by IMD 106, e.g., to force the Gamma band signalback into the homeostatic window and thereby suppress or partiallysuppress side effects. Further, while the magnitude of the monitoredneurological signal remains within the homeostatic window, or when themagnitude of the monitored neurological signal returns to thehomeostatic window, IMD 106 maintains the present magnitudes of theparameters defining the electrical stimulation. However, in thisexample, the IMD 106 is configured to ensure that any adjustments to theone or more parameters are within the bounds of the therapeutic window.

In further examples, IMD 106 determines a transformation of theneurological signal so as to determine a probability that the patientwill experience an event, such as a seizure or a fall. In such anexample, the clinician may set the upper bound and the lower bound ofthe homeostatic window to correspond to a maximum probability and aminimum probability that the patient will experience the event. Forexample, IMD 106 may reduce a magnitude of a parameter, such as acurrent or voltage amplitude of the electrical stimulation therapy, inresponse to the transformation falling below the lower bound of thehomeostatic window. In this case, the transformation falling below thelower bound may indicate decreased probability that the patient willexperience the event, such that stimulation parameter magnitude isreduced by IMD 106. Alternatively, IMD 106 may increase a magnitude of aparameter, such as a current or voltage amplitude of the electricalstimulation therapy, in response to the transformation exceeding theupper bound of the homeostatic window. In this case, the transformationexceeding the upper bound may indicate an increased probability that thepatient will experience the event, such that stimulation parametermagnitude is increased by IMD 106.

In further examples, instead of, or in addition to, a neurologicalsignal of patient 112, IMD 106 monitors, via one or more sensors, aphysiological parameter. For example, the clinician may set lower andupper bounds for the homeostatic window using a sensed parameterindicative of tremor of patient 112 instead of a neurological signal.The IMD 106 may monitor, via an accelerometer, a tremor of patient 112.Accordingly, IMD 106, in response to variations in a monitored tremorsignal, e.g., such as real-time or near real-time variations inamplitude or frequency of the tremor, may deliver adaptive DBS topatient 112 by adjusting the magnitude of one or more parametersdefining the electrical stimulation therapy, such as the voltage orcurrent amplitude of electrical stimulation pulses. For example, IMD 106may reduce a magnitude of a parameter, such as a current or voltageamplitude of the electrical stimulation therapy, in response to themagnitude of a physiological parameter signal from an accelerometer, orother sensor, indicative of the tremor in patient 112 falling below thelower bound of the homeostatic window. In this case, the tremor signalfalling below the lower bound may indicate a reduction in symptoms, suchthat stimulation parameter magnitude is reduced by IMD 106.Alternatively, IMD 106 may increase a magnitude of a parameter, such asa current or voltage amplitude of the electrical stimulation therapy, inresponse to the magnitude of a physiological parameter signal from anaccelerometer indicative of the tremor in patient 112 exceeding theupper bound of the homeostatic window. In this case, the tremor signalexceeding the upper bound may indicate an increase in symptoms, suchthat stimulation parameter magnitude is increased by IMD 106. Further,while a signal from an accelerometer indicative of the tremor in patient112 remains within the homeostatic window, or when the magnitude ofsignal from an accelerometer indicative of the tremor in patient 112returns to the homeostatic window, IMD 106 maintains the presentmagnitudes of the parameters defining the electrical stimulation.However, IMD 106 ensures that any adjustments to the one or moreparameters are within the bounds of the therapeutic window.

System 100 may use the therapeutic window to define an upper bound and alower bound for one or more parameters defining the adaptive DBS. Forexample, system 100 may adjust current or voltage amplitude of theelectrical stimulation therapy in response to patient input to thehomeostatic window or variations in a sensed signal, but maintain themagnitude to be within a magnitude range defined by an upper magnitudebound and a lower magnitude bound of the therapeutic window. Typically,a clinician may set an upper bound for the therapeutic window as amaximum of one or more parameters defining the electrical stimulation.In an example of a voltage-controlled system, the clinician sets theupper bound of the therapeutic window as a maximum voltage amplitude ofthe electrical stimulation that the system may not exceed. In an exampleof a current-controlled system, the clinician sets the upper bound ofthe therapeutic window as a maximum current amplitude of the electricalstimulation that the system may not exceed. Typically, the upper boundof the therapeutic window is a maximum safe magnitude of thestimulation. In other words, the upper bound of the therapeutic windowis a magnitude substantially below a pain threshold or a tissue injurythreshold. In some examples, a clinician may alternatively oradditionally determine the maximum safe magnitude to be a magnitude ofthe stimulation that does not cause side effects, or an undesirabledegree of side effects, in the patient. However, in some cases, theupper bound of the therapeutic window is the highest magnitude of thestimulation that does not cause discomfort to the patient.

A clinician may set a lower bound for the therapeutic window as aminimum of one or more parameters defining the electrical stimulation.In one example, a clinician sets the lower bound for the therapeuticwindow to correspond to a minimum magnitude of stimulation that, whendelivered at a continuous magnitude and frequency, is sufficient tosuppress symptoms of the patient to at least a minimum degree on asubstantially continuous basis. In an example of a voltage-controlledsystem, the clinician sets the lower bound of the therapeutic window asa minimum voltage amplitude of the electrical stimulation that thesystem should continuously provide to the patient. In an example of acurrent-controlled system, the clinician sets the lower bound of thetherapeutic window as a minimum current amplitude of the electricalstimulation that the system should continuously provide to the patientfor therapy. In some examples, the lower and upper bounds are inclusive(i.e., system 106 may select parameters defining the electricalstimulation within a range of values that are greater than or equal tothe lower bound and less than or equal to the upper bound), while inother examples, the lower and upper bounds are exclusive (i.e., system106 may select parameters defining the electrical stimulation within arange of values that are greater than but not equal to the lower boundand less than but not equal to the upper bound). Furthermore, while thepatient may adjust the upper and lower bound of the homeostatic windowto indirectly control one or more parameters defining the electricalstimulation, the patient typically is not permitted to adjust the upperand lower bound of the therapeutic window, e.g., out of safety concerns.

Thus, system 100, via IMD 106, by sensing the signal of the patient andadjusting one or more parameters of the electrical stimulation therapysuch that the sensed signal remains within the homeostatic window,delivers electrical stimulation therapy that is adaptive, i.e., therapythat is moderated to the real-time severity of the one or more symptomsof patient 112. Thus, upon detecting that the severity of the one ormore symptoms of patient 112 is increasing, e.g., as indicated bypatient input sensed neurological signals, and/or sensed physiologicalparameter signals exceeding the upper bound of an applicable homeostaticwindow or windows, system 100 may ramp up the magnitude of one or moreparameters defining the electrical stimulation therapy to ensure thatthe one or more symptoms of patient 112 remain controlled. Furthermore,upon detecting that the severity of the one or more symptoms of patient112 is decreasing, e.g., as indicated by patient input, sensedneurological signals, and/or sensed physiological parameter signals,falling below the lower bound of the homeostatic window, system 100 mayramp down the magnitude of the one or more parameters defining theelectrical stimulation therapy to reduce the likelihood of side effectsto patient 112, as well as decrease power consumption and enhance thebattery life of the IMD 106. Again, as an example, the one or moreparameters may include current amplitude (for current-controlledsystems) or voltage amplitude (for voltage-controlled systems) ofstimulation.

As described above, the lower bound of the homeostatic window is set atthe magnitude of the sensed signal, e.g., neurological signal orphysiological parameter signal, during the minimum magnitude ofelectrical stimulation that was sufficient to prevent break-through ofthe symptoms of the patient while the patient was on medication.Further, the upper bound of the homeostatic window is set at themagnitude of the signal at which, while the patient was off medication(as described above), further increase to the magnitude of one or moreparameters defining the electrical stimulation therapy does not cause afurther reduction in the severity of the symptoms. Although, in someexamples, the upper bound of the homeostatic window is set at themagnitude of the signal when electrical stimulation having a maximummagnitude of the one or more parameters is delivered to patient 112. Byusing the homeostatic window to heuristically define an upper bound anda lower bound as thresholds for adjusting the one or more parametersdefining the electrical stimulation, the system 100 may ensure, via thelower and upper bounds of the homeostatic window, that the sensedsignal, e.g., sensed neurological signal or sensed physiologicalparameter signal, floats within a range of expected behavior, and onlytriggers IMD 106 to make an adjustment to the one or more parametersdefining the electrical stimulation when the signal deviates from theexpected behavior.

Furthermore, the system 100 ensures, via the lower bound of thetherapeutic window, that system 100 does not reduce the magnitude ofelectrical stimulation below a minimum magnitude that the cliniciandetermined should be continuously delivered to the patient.Additionally, the system 100 ensures, via the upper bound of thetherapeutic window, that system 100 does not increase the magnitude ofelectrical stimulation above a maximum magnitude that the cliniciandetermined is safe and/or comfortable for the patient. By permittingadaptive adjustment of one or more stimulation parameters to maintainthe sensed neurological signal or physiological parameter signal toremain in the homeostatic window, while constraining the values of theone or more parameters to reside within a range of values from the lowerbound to the upper bound of the therapeutic window, system 100 maypromote therapeutic efficacy and/or power efficiency. Further, thesystem 100 may avoid continuously adjusting, throttling, or oscillatingthe one or more stimulation parameters, avoiding excessive power drainon the system 100 without providing further treatment of the symptoms ofthe patient.

In another example, instead of the clinician, system 100 automaticallydefines parameters for the upper bound of the homeostatic window. Inthis example, sensors 109A-109B (collectively, “sensors 109”) of system100 measure the one or more symptoms while the patient 112 is offmedication for the one or more symptoms. For example, sensors 109 mayinclude one or more accelerometers for sensing signals used byprogrammer 104 or IMD 106 to determine rigidity due to Parkinson'sdisease by measuring wrist flexion of patient 112. Alternatively, thesensors 109 may include accelerometers for sensing signals used byprogrammer 104 or IMD 106 to measure the severity of tremors due toParkinson's disease. IMD 106, in response to commands from externalprogrammer 104, increases the one or more parameters until theelectrical stimulation reduces the one or more symptoms to apredetermined threshold. In another example, IMD 106, in response tocommands from external programmer 104, increases the one or moreparameters until a point at which increasing the magnitude of the one ormore parameters does not cause further alleviation of the one or moresymptoms. For example, programmer 104 may issue instructions to IMD 106causing IMD 106 to increase the magnitude of one or more parameters ofelectrical stimulation therapy until the rigidity or tremors of patient112 are eliminated or reduced by a predetermined degree, and thesymptoms thereby reduced. Accordingly, programmer 104 measures themagnitude of the sensed signal, for example, the magnitude of beta inthe brain 120 of patient 112 when the rigidity or tremors are eliminatedor reduced by a predetermined degree, and sets this magnitude as theupper bound of the homeostatic window.

In another example, instead of the clinician, system 100 automaticallydefines parameters for the lower bound of the homeostatic window. Inthis example, sensors 109A-109B (collectively, “sensors 109”) of system100 measure the one or more symptoms while the patient 112 is onmedication for the one or more symptoms (as described above). Asdescribed above, sensors 109 may include one or more accelerometers forsensing signals used by programmer 104 or IMD 106 to determine rigiditydue to Parkinson's disease by measuring wrist flexion of patient 112.Alternatively, the sensors 109 may include accelerometers for sensingsignals used by programmer 104 or IMD 106 to measure the severity oftremors due to Parkinson's disease. IMD 106, in response to commandsfrom external programmer 104, decreases the one or more parameters untilthe electrical stimulation fails to treat the one or more symptoms. Forexample, the IMD 106 may decrease the one or more parameters until thesymptoms of the patient 112 emerge, or until the severity of thesymptoms increases to a predetermined threshold. For example, programmer104 may issue instructions to IMD 106 causing IMD 106 to decrease themagnitude of one or more parameters of electrical stimulation therapyuntil the rigidity or tremors of patient 112 returns, or increases to apredetermined degree. Accordingly, programmer 104 measures the magnitudeof the signal, for example, the magnitude of a neurological signalwithin the Beta frequency band in the brain 120 of patient 112, at apoint which symptoms emerge or increase to a predetermined threshold,and sets this magnitude as the lower bound of the homeostatic window.

In the foregoing example, the one or more symptoms were symptoms ofParkinson's disease. However, in other implementations of the techniquesof the disclosure, the one or more symptoms are symptoms resulting fromother disorders, such as depression, epilepsy, chronic pain, or thelike.

Additionally, in one example, patient 112, via external programmer 104,may provide feedback to adjust one or more bounds of the homeostaticwindow. For example, if patient 112 determines that the electricalstimulation therapy is not treating or not sufficiently treating the oneor more symptoms of patient 112 effectively, patient 112 may providefeedback causing external programmer 104 to shift downward the upperbound of the homeostatic window, or shift the entire homeostatic windowitself downward. To drive the signal to a lower window, the systemincreases the one or more parameters of the electrical stimulationtherapy, and thereby increases the magnitude of electrical stimulationtherapy to reduce the symptoms of the patient. In another example, ifpatient 112 determines that the electrical stimulation therapy isunpleasant, causes side effects, or is otherwise uncomfortable topatient 112, patient 112 may provide feedback causing externalprogrammer 104 to shift upward the lower bound of the homeostaticwindow, or the shift entire homeostatic window itself upward. This hasthe effect of allowing the signal to float to a lower window,effectively causing the system 100 to decrease the one or moreparameters of the electrical stimulation therapy, and thereby decreasesthe magnitude of electrical stimulation therapy to reduce side effects.While the patient 112 may adjust one or more bounds of the homeostaticwindow, or the homeostatic window itself, to ensure the safety of thepatient, the patient 112 may not alter the therapeutic window that setslower and upper bounds for the one or more parameters of the electricalstimulation therapy.

In another example, sensors 109 detect a physiological parameter of thepatient, and in response to the physiological parameter, externalprogrammer 104 automatically issues commands to IMD 106 to adjust one orboth bounds of the homeostatic window. For example, in response tosignals from sensors 109, external programmer 104 may determine that themagnitude of one or more parameters defining the electrical stimulationtherapy is insufficient to reduce the one or more symptoms of patient112. In this example, external programmer 104 may issue instructions toIMD 106 to shift downward the upper bound of the homeostatic window, orshift the entire homeostatic window itself downward. To drive the signalto a lower window, the system 100 effectively increases the one or moreparameters of the electrical stimulation therapy, and thereby increasesthe magnitude of electrical stimulation therapy to reduce the symptomsof the patient. In another example, in response to signals from sensors109, external programmer 104 may determine that, based on a symptom ofthe patient (e.g., tremor, rigidity, or wrist flexion), a posture of thepatient (e.g., laying, sitting, standing, etc.) or an activity level ofthe patient (i.e., sleeping, walking, exercising, etc.), externalprogrammer 104 should adjust the magnitude of one or more parametersdefining the electrical stimulation therapy. External programmer 104 mayissue instructions to IMD 106 to adjust the lower bound of thehomeostatic window, the upper bound of the homeostatic window, or theentire homeostatic window itself. By allowing the signal to float atdifferent magnitudes, system 100 effectively adjusts the one or moreparameters of the electrical stimulation therapy, and thereby adjuststhe magnitude of electrical stimulation therapy to compensate fordifferent activity levels of patient 112. Typically, system 100 may notresize the therapeutic window beyond safety guidelines set by theclinician, which may be expressed as a maximum adjustment to upperbound, lower bound, or window shift, either in an absolute sense or inthe sense of a maximum adjustment per unit time.

In some examples, each of sensors 109 is an accelerometer, a bondedpiezoelectric crystal, a mercury switch, or a gyro. In some examples,sensors 109 may provide a signal that indicates a physiologicalparameter of the patient, which in turn varies as a function of patientactivity. For example, the device may monitor a signal that indicatesthe heart rate, electrocardiogram (ECG) morphology, electroencephalogram(EEG) morphology, respiration rate, respiratory volume, coretemperature, subcutaneous temperature, or muscular activity of thepatient.

In some examples, sensors 109 generate a signal both as a function ofpatient activity and patient posture. For example, accelerometers,gyros, or magnetometers may generate signals that indicate both theactivity and the posture of a patient 112. External programmer 104 mayuse such information regarding posture to determine whether externalprogrammer 104 should perform adjustments to the therapeutic window.

For example, in order to identify posture, sensors 109 such asaccelerometers may be oriented substantially orthogonally with respectto each other. In addition to being oriented orthogonally with respectto each other, each of sensors 109 used to detect the posture of apatient 112 may be substantially aligned with an axis of the body of apatient 112. When accelerometers, for example, are aligned in thismanner, the magnitude and polarity of DC components of the signalsgenerate by the accelerometers indicate the orientation of the patientrelative to the Earth's gravity, e.g., the posture of a patient 112.Further information regarding use of orthogonally aligned accelerometersto determine patient posture may be found in a commonly assigned U.S.Pat. No. 5,593,431, which issued to Todd J. Sheldon, the entire contentof which is incorporated by reference herein.

Other sensors 109 that may generate a signal that indicates the postureof a patient 112 include electrodes that generate a signal as a functionof electrical activity within muscles of a patient 112, e.g., anelectromyogram (EMG) signal, or a bonded piezoelectric crystal thatgenerates a signal as a function of contraction of muscles. Electrodesor bonded piezoelectric crystals may be implanted in the legs, buttocks,chest, abdomen, or back of a patient 112, and coupled to one or more ofexternal programmer 104 and IMD 106 wirelessly or via one or more leads.Alternatively, electrodes may be integrated in a housing of the IMD 106or piezoelectric crystals may be bonded to the housing when IMD 106 isimplanted in the buttocks, chest, abdomen, or back of a patient 112. Thesignals generated by such sensors when implanted in these locations mayvary based on the posture of a patient 112, e.g., may vary based onwhether the patient is standing, sitting, or lying down.

Further, the posture of a patient 112 may affect the thoracic impedanceof the patient. Consequently, sensors 109 may include an electrode pair,including one electrode integrated with the housing of IMDs 106 and oneof electrodes 116, 118, that generate a signal as a function of thethoracic impedance of a patient 112, and IMD 106 may detect the postureor posture changes of a patient 112 based on the signal. In one example(not depicted), the electrodes of the pair may be located on oppositesides of the patient's thorax. For example, the electrode pair mayinclude electrodes located proximate to the spine of a patient fordelivery of SCS therapy, and IMD 106 with an electrode integrated in itshousing may be implanted in the abdomen or chest of patient 112. Asanother example, IMD 106 may include electrodes implanted to detectthoracic impedance in addition to leads 114 implanted within the brainof patient 112. The posture or posture changes may affect the deliveryof DBS or SCS therapy to patient 112 for the treatment of any type ofneurological disorder, and may also be used to detect patient sleep, asdescribed herein.

Additionally, changes of the posture of a patient 112 may cause pressurechanges with the cerebrospinal fluid (CSF) of the patient. Consequently,sensors 109 may include pressure sensors coupled to one or moreintrathecal or intracerebroventricular catheters, or pressure sensorscoupled to IMDs 106 wirelessly or via one of leads 114. CSF pressurechanges associated with posture changes may be particularly evidentwithin the brain of the patient, e.g., may be particularly apparent inan intracranial pressure (ICP) waveform.

Accordingly, in some examples, instead of monitoring a neurologicalsignal of the patient, the system 100 monitors one or more signals fromsensors 109 indicative of a magnitude of a physiological parameter ofpatient 112. Upon detecting that one or more signals from sensors 109exceed the upper bound of the homeostatic window, the system 100increases stimulation at a maximum ramp rate determined by the clinicianuntil one or more signals from sensors 109 return to within thehomeostatic window, or until the magnitude of the electrical stimulationreaches an upper limit of a therapeutic window determined by theclinician. Similarly, upon detecting that one or more signals fromsensors 109 falls below the lower bound of the homeostatic window, thesystem decreases stimulation at a maximum ramp rate determined by theclinician until one or more signals from sensors 109 return to withinthe homeostatic window, or until the magnitude of the electricalstimulation reaches a lower limit of a therapeutic window determined bythe clinician. Upon detecting that one or more signals from sensors 109is within the bounds of the homeostatic window, the system holds themagnitude of the electrical stimulation constant.

Such a system 100 for delivering adaptive DBS to the patient bymonitoring a physiological parameter may provide advantages over othertechniques that use a neurological signal as a threshold in that thetechniques of the disclosure allow an IMD to control delivery of therapyusing hysteresis. In other words, such a system 100 uses thephysiological parameter of the patient to create a control loop for notonly controlling the delivery of therapy, but also controlling themagnitude of the delivered therapy. Such a system may be less intrusiveon the activity of a patient because the system 100 adapts thestimulation to the current needs of the patient, and thus may reduce theside effects that the patient experiences.

Further, such a system 100 may use external sensors, such asaccelerometers, instead of internal sensors, such as electrodes, todetect symptoms of the disease of the patient and control adjustments tothe magnitude of one or more parameters of the therapy. For example, thesystem 100 may use a wrist sensor to detect wrist flexion or tremor of apatient suffering from Parkinson's disease. Thus, such an IMD themonitoring of a physiological parameter may be less invasive than otherIMD systems because the system of the present disclosure may not requiresensing electrodes to be implanted in the brain of the patient 112.

In some circumstances, system 100, as described herein, may deliver,based on the upper and lower bounds of the homeostatic window, a lowermagnitude of electrical stimulation than patient 112 requires to preventbreakthrough of his or her symptoms. For example, a patient receivingtherapy from an IMD 106 that controls delivery of electrical stimulationtherapy using the homeostatic window may, in certain circumstances,experience results that are less optimal than if the patient receivedcontinuous electrical stimulation therapy at a maximum therapymagnitude. To prevent this occurrence, system 100 may determine a valuefor the at least one electrical stimulation parameter as defined by thehomeostatic window, as described above. Further, the IMD 106 of system100 may increase the value for the at least one electrical stimulationparameter by a bias amount greater than the determined magnitude definedby the homeostatic window so as to further prevent breakthrough of thesymptoms of patient 112. Thus, system 100 may avoid deliveringelectrical stimulation therapy that is of a magnitude that may beinsufficient for prevention of symptom breakthrough.

As one example of the biasing techniques described above, IMD 106 maydetermine an average value over time for the at least one parameter ofthe electrical stimulation (e.g., an average value over time of avoltage amplitude or a current amplitude) as defined by an averagemagnitude of the sensed signal within the homeostatic window. IMD 106may further determine a bias amount for the at least one parameter ofthe electrical stimulation. In one example, the bias amount is adifference between the average value for the at least one parameter ofthe electrical stimulation, e.g., voltage or current amplitude, asdefined by the average magnitude of the sensed signal, and a value forthe at least one stimulation therapy parameter for an equivalentcontinuous (e.g., non-adaptive) electrical stimulation therapycontinuously provided to the patient. In an example of acurrent-controlled system, the at least one parameter of the electricalstimulation is current amplitude, and the bias amount may be, forexample, selected from a range of about 0.1 milliamps to about 5milliamps (e.g., about 1 milliamp). In an example of avoltage-controlled system, the at least one parameter of the electricalstimulation is voltage amplitude, and the bias amount may be, forexample, selected from a range of about 0.1 Volts to about 5 Volts(e.g., about 1 Volt). Upon delivering the electrical stimulationtherapy, IMD 106 increases the value for the at least one parameter ofthe electrical stimulation as defined by the homeostatic window by thebias amount. In this fashion, IMD 106 may deliver electrical stimulationtherapy with one or more stimulation parameter values selected tomaintain the sensed phycological parameter or neurological signal withinthe homeostatic window while ensuring that the electrical stimulationtherapy is as effective as continuous electrical stimulation therapydelivered at a maximum therapy magnitude.

In some examples, IMD 106 may determine the average value for the atleast one parameter of the electrical stimulation and the bias amount ona periodic basis, such as a time period selected from a range of 1second to 24 hours (e.g., every 30 seconds or every 10 minutes). Inanother example, the time period may correlate to a time course ofmedication and may be about 10 minutes to about 15 minutes. In otherexamples, a clinician may program the bias amount into a memory of IMD106 or programmer 104. In such an example, the clinician may program themagnitude of the bias amount, such as selecting a magnitude for the biasamount from a range of bias amounts of about 0.5 milliamps to about 5milliamps in a current controlled system. In another example, theclinician may specify how often the determination is performed, such asprogramming IMD 106 to recalculate the average value and the bias amountonce after the expiration of a period of time selected from a range ofabout 10 seconds to 1 hour. In yet another example, the clinician mayspecify the length of time included in the determination of the averagevalue of the stimulation parameter, such as averaging values for the atleast one parameter of the electrical stimulation during a period oftime selected from a range of the previous 20 seconds to the previous 5minutes.

The architecture of system 100 illustrated in FIG. 1 is shown as anexample. The techniques as set forth in this disclosure may beimplemented in the example system 100 of FIG. 1 , as well as other typesof systems not described specifically herein. For example, a clinicianmay determine the upper bound and lower bound of the homeostatic window.In other examples, one of the external programmer 104 and IMD 104determines the upper bound and lower bound of the homeostatic window.Furthermore, either external programmer 104 or IMD 106 may receive thesignal representative of the signal of patient 112 and determine anadjustment to one or more parameters defining the electrical stimulationtherapy that IMD 106 delivers to patient 112. Nothing in this disclosureshould be construed so as to limit the techniques of this disclosure tothe example architecture illustrated by FIG. 1 .

FIG. 2 is a block diagram of the example IMD 106 of FIG. 1 fordelivering adaptive deep brain stimulation therapy. In the example shownin FIG. 2 , IMD 106 includes processor 210, memory 211, stimulationgenerator 202, sensing module 204, switch module 206, telemetry module208, sensor 212, and power source 220. Each of these modules may be orinclude electrical circuitry configured to perform the functionsattributed to each respective module. For example, processor 210 mayinclude processing circuitry, switch module 206 may include switchcircuitry, sensing module 204 may include sensing circuitry, andtelemetry module 208 may include telemetry circuitry. Memory 211 mayinclude any volatile or non-volatile media, such as a random-accessmemory (RAM), read only memory (ROM), non-volatile RAM (NVRAM),electrically erasable programmable ROM (EEPROM), flash memory, and thelike. Memory 211 may store computer-readable instructions that, whenexecuted by processor 210, cause IMD 106 to perform various functions.Memory 211 may be a storage device or other non-transitory medium.

In the example shown in FIG. 2 , memory 211 stores therapy programs 214and sense electrode combinations and associated stimulation electrodecombinations 218 in separate memories within memory 211 or separateareas within memory 211. Each stored therapy program 214 defines aparticular set of electrical stimulation parameters (e.g., a therapyparameter set), such as a stimulation electrode combination, electrodepolarity, current or voltage amplitude, pulse width, and pulse rate. Insome examples, individual therapy programs may be stored as a therapygroup, which defines a set of therapy programs with which stimulationmay be generated. The stimulation signals defined by the therapyprograms of the therapy group may be delivered together on anoverlapping or non-overlapping (e.g., time-interleaved) basis.

Sense and stimulation electrode combinations 218 stores sense electrodecombinations and associated stimulation electrode combinations. Asdescribed above, in some examples, the sense and stimulation electrodecombinations may include the same subset of electrodes 116, 118, ahousing of IMD 106 functioning as an electrode, or may include differentsubsets or combinations of such electrodes. Thus, memory 211 can store aplurality of sense electrode combinations and, for each sense electrodecombination, store information identifying the stimulation electrodecombination that is associated with the respective sense electrodecombination. The associations between sense and stimulation electrodecombinations can be determined, e.g., by a clinician or automatically byprocessor 210. In some examples, corresponding sense and stimulationelectrode combinations may comprise some or all of the same electrodes.In other examples, however, some or all of the electrodes incorresponding sense and stimulation electrode combinations may bedifferent. For example, a stimulation electrode combination may includemore electrodes than the corresponding sense electrode combination inorder to increase the efficacy of the stimulation therapy. In someexamples, as discussed above, stimulation may be delivered via astimulation electrode combination to a tissue site that is differentthan the tissue site closest to the corresponding sense electrodecombination but is within the same region, e.g., the thalamus, of brain120 in order to mitigate any irregular oscillations or other irregularbrain activity within the tissue site associated with the senseelectrode combination.

Stimulation generator 202, under the control of processor 210, generatesstimulation signals for delivery to patient 112 via selectedcombinations of electrodes 116, 118. An example range of electricalstimulation parameters believed to be effective in DB S to manage amovement disorder of patient include:

1. Pulse Rate, i.e., Frequency: between approximately 40 Hertz andapproximately 500 Hertz, such as between approximately 40 to 185 Hertzor such as approximately 140 Hertz.

2. In the case of a voltage controlled system, Voltage Amplitude:between approximately 0.1 volts and approximately 50 volts, such asbetween approximately 2 volts and approximately 3 volts.

3. In the alternative case of a current controlled system, CurrentAmplitude: between approximately 0.2 milliamps to approximately 100milliamps, such as between approximately 1.3 milliamps and approximately2.0 milliamps.

4. Pulse Width: between approximately 10 microseconds and approximately5000 microseconds, such as between approximately 100 microseconds andapproximately 1000 microseconds, or between approximately 180microseconds and approximately 450 microseconds.

Accordingly, in some examples, stimulation generator 202 generateselectrical stimulation signals in accordance with the electricalstimulation parameters noted above, subject to application of the upperand lower bounds of a therapeutic window to one or more of theparameters, such that an applicable parameter resides within the rangeprescribed by the window. Other ranges of therapy parameter values mayalso be useful, and may depend on the target stimulation site withinpatient 112. While stimulation pulses are described, stimulation signalsmay be of any form, such as continuous-time signals (e.g., sine waves)or the like.

Processor 210 may include fixed function processing circuitry and/orprogrammable processing circuitry, and may comprise, for example, anyone or more of a microprocessor, a controller, a digital signalprocessor (DSP), an application specific integrated circuit (ASIC), afield-programmable gate array (FPGA), discrete logic circuitry, or anyother processing circuitry configured to provide the functionsattributed to processor 210 herein may be embodied as firmware,hardware, software or any combination thereof. Processor 210 may controlstimulation generator 202 according to therapy programs 214 stored inmemory 211 to apply particular stimulation parameter values specified byone or more of programs, such as voltage amplitude or current amplitude,pulse width, or pulse rate.

In the example shown in FIG. 2 , the set of electrodes 116 includeselectrodes 116A, 116B, 116C, and 116D, and the set of electrodes 118includes electrodes 118A, 118B, 118C, and 118D. Processor 210 alsocontrols switch module 206 to apply the stimulation signals generated bystimulation generator 202 to selected combinations of electrodes 116,118. In particular, switch module 204 may couple stimulation signals toselected conductors within leads 114, which, in turn, deliver thestimulation signals across selected electrodes 116, 118. Switch module206 may be a switch array, switch matrix, multiplexer, or any other typeof switching module configured to selectively couple stimulation energyto selected electrodes 116, 118 and to selectively sense neurologicalbrain signals with selected electrodes 116, 118. Hence, stimulationgenerator 202 is coupled to electrodes 116, 118 via switch module 206and conductors within leads 114. In some examples, however, IMD 106 doesnot include switch module 206.

Stimulation generator 202 may be a single channel or multi-channelstimulation generator. In particular, stimulation generator 202 may becapable of delivering a single stimulation pulse, multiple stimulationpulses, or a continuous signal at a given time via a single electrodecombination or multiple stimulation pulses at a given time via multipleelectrode combinations. In some examples, however, stimulation generator202 and switch module 206 may be configured to deliver multiple channelson a time-interleaved basis. For example, switch module 206 may serve totime divide the output of stimulation generator 202 across differentelectrode combinations at different times to deliver multiple programsor channels of stimulation energy to patient 112. Alternatively,stimulation generator 202 may comprise multiple voltage or currentsources and sinks that are coupled to respective electrodes to drive theelectrodes as cathodes or anodes. In this example, IMD 106 may notrequire the functionality of switch module 206 for time-interleavedmultiplexing of stimulation via different electrodes.

Electrodes 116, 118 on respective leads 114 may be constructed of avariety of different designs. For example, one or both of leads 114 mayinclude two or more electrodes at each longitudinal location along thelength of the lead, such as multiple electrodes at different perimeterlocations around the perimeter of the lead at each of the locations A,B, C, and D. On one example, the electrodes may be electrically coupledto switch module 206 via respective wires that are straight or coiledwithin the housing the lead and run to a connector at the proximal endof the lead. In another example, each of the electrodes of the lead maybe electrodes deposited on a thin film. The thin film may include anelectrically conductive trace for each electrode that runs the length ofthe thin film to a proximal end connector. The thin film may then bewrapped (e.g., a helical wrap) around an internal member to form thelead 114. These and other constructions may be used to create a leadwith a complex electrode geometry.

Although sensing module 204 is incorporated into a common housing withstimulation generator 202 and processor 210 in FIG. 2 , in otherexamples, sensing module 204 may be in a separate housing from IMD 106and may communicate with processor 210 via wired or wirelesscommunication techniques. Example neurological brain signals include,but are not limited to, a signal generated from local field potentials(LFPs) within one or more regions of brain 28. EEG and ECoG signals areexamples of local field potentials that may be measured within brain120. However, local field potentials may include a broader genus ofelectrical signals within brain 120 of patient 112.

Sensor 212 may include one or more sensing elements that sense values ofa respective patient parameter. For example, sensor 212 may include oneor more accelerometers, optical sensors, chemical sensors, temperaturesensors, pressure sensors, or any other types of sensors. Sensor 212 mayoutput patient parameter values that may be used as feedback to controldelivery of therapy. IMD 106 may include additional sensors within thehousing of IMD 106 and/or coupled via one of leads 114 or other leads.In addition, IMD 106 may receive sensor signals wirelessly from remotesensors via telemetry module 208, for example. In some examples, one ormore of these remote sensors may be external to patient (e.g., carriedon the external surface of the skin, attached to clothing, or otherwisepositioned external to the patient).

Telemetry module 208 supports wireless communication between IMD 106 andan external programmer 104 or another computing device under the controlof processor 210. Processor 210 of IMD 106 may receive, as updates toprograms, values for various stimulation parameters such as magnitudeand electrode combination, from programmer 104 via telemetry module 208.The updates to the therapy programs may be stored within therapyprograms 214 portion of memory 211. Telemetry module 208 in IMD 106, aswell as telemetry modules in other devices and systems described herein,such as programmer 104, may accomplish communication by radiofrequency(RF) communication techniques. In addition, telemetry module 208 maycommunicate with external medical device programmer 104 via proximalinductive interaction of IMD 106 with programmer 104. Accordingly,telemetry module 208 may send information to external programmer 104 ona continuous basis, at periodic intervals, or upon request from IMD 106or programmer 104.

Power source 220 delivers operating power to various components of IMD106. Power source 220 may include a small rechargeable ornon-rechargeable battery and a power generation circuit to produce theoperating power. Recharging may be accomplished through proximalinductive interaction between an external charger and an inductivecharging coil within IMD 220. In some examples, power requirements maybe small enough to allow IMD 220 to utilize patient motion and implementa kinetic energy-scavenging device to trickle charge a rechargeablebattery. In other examples, traditional batteries may be used for alimited period of time.

According to the techniques of the disclosure, processor 210 of IMD 106delivers, electrodes 116, 118 interposed along leads 114 (and optionallyswitch module 206), electrical stimulation therapy to patient 112. Theadaptive DBS therapy is defined by one or more therapy programs 214having one or more parameters stored within memory 211. For example, theone or more parameters include a current amplitude (for acurrent-controlled system) or a voltage amplitude (for avoltage-controlled system), a pulse rate or frequency, and a pulsewidth., or a number of pulses per cycle. In examples where theelectrical stimulation is delivered according to a “burst” of pulses, ora series of electrical pulses defined by an “on-time” and an “off-time,”the one or more parameters may further define one or more of a number ofpulses per burst, an on-time, and an off-time. In one example, thetherapeutic window defines an upper bound and a lower bound for avoltage amplitude of the electrical stimulation therapy. In anotherexample, the therapeutic window defines an upper bound and a lower boundfor a current amplitude of the electrical stimulation therapy. Inparticular, a parameter of the electrical stimulation therapy, such asvoltage or current amplitude, is constrained to a therapeutic windowhaving an upper bound and a lower bound, such that the voltage orcurrent amplitude may be adjusted provided the amplitude remains greaterthan or equal to the lower bound and less than or equal to the upperbound.

In one example, processor 210, via electrodes 116, 118 of IMD 106,monitors the behavior of a signal of patient 112 that correlates to oneor more symptoms of a disease of patient 112 within a homeostaticwindow. Processor 210, via electrodes 116, 118, delivers to patient 112adaptive DBS and may adjust one or more parameters defining theelectrical stimulation within a parameter range defined by lower andupper bounds of a therapeutic window based on the activity of the sensedsignal within the homeostatic window.

In one example, the signal is a neurological signal within the Betafrequency band of brain 120 of patient 112. The signal within the Betafrequency band of patient 112 may correlate to one or more symptoms ofParkinson's disease in patient 112. Generally speaking, neurologicalsignals within the Beta frequency band of patient 112 may beapproximately proportional to the severity of the symptoms of patient112. For example, as tremor induced by Parkinson's disease increases,one or more of electrodes 116, 118 detect an increase in the magnitudeof neurological signals within the Beta frequency band of patient 112.

Similarly, as tremor induced by Parkinson's disease decreases, processor210, via the one or more of electrodes 116, 118, detects a decrease inthe magnitude of the neurological signals within the Beta frequency bandof patient 112. In another example, the signal is a neurological signalwithin the Gamma frequency band of brain 120 of patient 112. The signalwithin the Gamma frequency band of patient 112 may also correlate to oneor more side effects of the electrical stimulation therapy. However, incontrast to neurological signals within the Beta frequency band,generally speaking, neurological signals within the Gamma frequency bandof patient 112 may be approximately inversely proportional to theseverity of the side effects of the electrical stimulation therapy. Forexample, as side effects due to electrical stimulation therapy increase,processor 210, via the one or more of electrodes 116, 118, detects adecrease in the magnitude of the signal within the Gamma frequency bandof patient 112. Similarly, as side effects due to electrical stimulationtherapy decrease, processor 210, via the one or more of electrodes 116,118, detects an increase in the magnitude of the signal within the Gammafrequency band of patient 112.

In response to detecting that the signal of the patient, e.g., a sensedphysiological parameter signal or a sensed neurological signal, hasdeviated from the homeostatic window, processor 210 dynamically adjuststhe magnitude of the one or more parameters of the electricalstimulation therapy such as, e.g., pulse current amplitude or pulsevoltage amplitude, to drive the signal of the patient back into thehomeostatic window. For example, wherein the signal is a neurologicalsignal within the Beta frequency band of brain 120 of patient 112,processor 210, via the one or more of electrodes 116, 118, monitors thebeta magnitude of patient 112. Upon detecting that the beta magnitude ofpatient 112 exceeds the upper bound of the homeostatic window, processor210 increases a magnitude of the electrical stimulation delivered viaelectrodes 116, 118 at a maximum ramp rate determined by the clinicianuntil the magnitude of the neurological signal within the Beta bandfalls back to within the homeostatic window, or until the magnitude ofthe electrical stimulation reaches an upper limit of a therapeuticwindow determined by the clinician. Similarly, upon detecting that thebeta magnitude of patient 112 falls below the lower bound of thehomeostatic window, processor 210 decreases stimulation magnitude at amaximum ramp rate determined by the clinician until the beta magnituderises back to within the homeostatic window, or until the magnitude ofthe electrical stimulation reaches a lower limit of a therapeutic windowdetermined by the clinician. Upon detecting that the beta magnitude ispresently within the bounds of the homeostatic window, or has returnedto within the bounds of the homeostatic window, processor 210 holds themagnitude of the electrical stimulation constant.

As another example, wherein the signal is a neurological signal withinthe Gamma frequency band of brain 120 of patient 112, processor 210, viathe one or more of electrodes 116, 118, monitors the gamma magnitude ofpatient 112. Upon detecting that the gamma magnitude of patient 112falls below the lower bound of the homeostatic window, processor 210increases a magnitude of the electrical stimulation delivered viaelectrodes 116, 118 at a maximum ramp rate determined by the clinicianuntil the gamma magnitude rises back to within the homeostatic window,or until the magnitude of the electrical stimulation reaches an upperlimit of a therapeutic window determined by the clinician. Similarly,upon detecting that the gamma magnitude of patient 112 rises above theupper bound of the homeostatic window, processor 210 decreasesstimulation at a maximum ramp rate determined by the clinician until thegamma magnitude falls back to within the homeostatic window, or untilthe magnitude of the electrical stimulation reaches a lower limit of atherapeutic window determined by the clinician. Upon detecting that thegamma magnitude is presently within the bounds of the homeostaticwindow, or has returned to within the bounds of the homeostatic window,processor 210 holds the magnitude of the electrical stimulationconstant.

In some examples, processor 210 continuously measures the signal in realtime. In other examples, processor 210 periodically samples the signalaccording to a predetermined frequency or after a predetermined amountof time. In some examples, processor 210 periodically samples the signalat a frequency of approximately 150 Hertz.

Furthermore, processor 210 delivers electrical stimulation therapy thatis constrained by an upper bound and a lower bound of a therapeuticwindow. In some examples, values defining the therapeutic window arestored within memory 211 of IMD 106. For example, in response todetecting that the signal has deviated from the homeostatic window,processor 210 of IMD 106 may adjust one or more parameters of theelectrical stimulation therapy to provide responsive treatment topatient 112. For example, in response to detecting that the signal hasexceeded an upper bound of the homeostatic window and prior todelivering the electrical stimulation therapy, processor 210 determineswhether the adjustment to the one or more parameters is greater than anupper bound of the therapeutic window, and if so, reduces the one ormore parameters to be at or below the magnitude of the upper bound. Forexample, in a voltage-controlled system wherein the clinician has setthe upper bound of the therapeutic window to be 3 Volts, processor 210determines whether the adjustment to the one or more parameters isgreater than 3 Volts, and if so, sets the adjustment to be 3 Volts.

In another example, in response to detecting that the signal has fallenbelow a lower bound of the homeostatic window and prior to deliveringthe electrical stimulation therapy, processor 210 determines whether theadjustment to the one or more parameters is less than a lower bound ofthe therapeutic window, and if so, increases the one or more parametersto be at or above the magnitude of the lower bound. For example, in theabove voltage-controlled system wherein the clinician has set the lowerbound of the therapeutic window to be 2 Volts, processor 210 determineswhether the adjustment to the one or more parameters is less than 2Volts, and if so, sets the adjustment to be 2 Volts. Thus, processor 210of IMD 106 may deliver adaptive DBS to patient 112 wherein the one ormore parameters describing the adaptive DBS is within the therapeuticwindow.

In the foregoing example, the bounds of the therapeutic window areinclusive (i.e., the upper and lower bounds are valid values for the oneor more parameters). However, in other examples, the bounds of thetherapeutic window are exclusive (i.e., the upper and lower bounds arenot valid values for the one or more parameters). In such an example ofan exclusive therapeutic window, processor 210 instead sets theadjustment to the one or more parameters to be the next highest validvalue (in the case of an adjustment potentially exceeding the upperbound) or the next lowest valid value (in the case of an adjustmentpotentially exceeding the lower bound).

In another example, values defining the therapeutic window are storedwithin a memory 311 of external programmer 104. In this example, inresponse to detecting that the signal has deviated from the homeostaticwindow, processor 210 of IMD 106 transmits, via telemetry module 208,data representing the measurement of the signal to external programmer104. In one example, in response to detecting that the signal hasexceeded an upper bound of the homeostatic window, processor 210 of IMD106 transmits, via telemetry module 208, data representing themeasurement of the signal to external programmer 104. Externalprogrammer 104 determines whether the adjustment to the one or moreparameters is greater than an upper bound of the therapeutic window, andif so, reduces the one or more parameters to be at or below themagnitude of the upper bound. For example, in a voltage-controlledsystem wherein the clinician has set the upper bound of the therapeuticwindow to be 3 Volts, external programmer 104 determines whether theadjustment to the one or more parameters is greater than 3 Volts, and ifso, instructs processor 210 of IMD 106 to set the adjustment to be 3Volts.

In another example, in response to detecting that the signal has fallenbelow a lower bound of the homeostatic window, processor 210 of IMD 106transmits, via telemetry module 208, data representing the measurementof the signal to external programmer 104. External programmer 104determines whether the adjustment to the one or more parameters is lessthan a lower bound of the therapeutic window, and if so, reduces the oneor more parameters to be at or above the magnitude of the lower bound.For example, in a voltage-controlled system wherein the clinician hasset the lower bound of the therapeutic window to be 2 Volts, externalprogrammer 104 determines whether the adjustment to the one or moreparameters is less than 2 Volts, and if so, instructs processor 210 ofIMD 106 to set the adjustment to be 2 Volts.

In another example, processor 210, via telemetry module 208 and fromexternal programmer 104, receives instructions to adjust to one or morebounds of the therapeutic window. For example, such instructions may bein response to patient feedback on the efficacy of the electricalstimulation therapy, or in response to one or more sensors 109 that havedetected a signal of the patient. Such signals from sensors 109 mayinclude neurological signals, such as a signal within the Beta frequencyband or signal within the Gamma frequency band of brain 120 of patient112, or physiological parameters and measurements, such as a signalindicating one or more of a patient activity level, posture, andrespiratory function. Further, such signals from sensors 109 mayindicate a lack of reduction of one or more symptoms of the patient 112,such as tremor or rigidity or the presence of side effects due toelectrical stimulation therapy, such as paresthesia. In response tothese instructions, processor 210 may adjust one or more bounds of thehomeostatic window. For example, processor 210 may adjust the magnitudeof the upper bound, the lower bound, or shift the overall position ofthe homeostatic window such that the threshold, defined by thehomeostatic window, for adjustment of the one or more parameters ofelectrical stimulation, is itself adjusted. Thereafter, processor 210,via electrodes 116 and 118, delivers the adjusted electrical stimulationto patient 112.

As one example, processor 210 receives, via telemetry module 208, aninput from sensors 109 indicating a magnitude of wrist flexion. If theinput indicates that the performance of the wrist flexion of patient 112is below a therapeutic magnitude determined by the clinician andprogrammed into IMD 106 via external programmer 104, processor 210adjusts the homeostatic window down. In some examples, processor 210adjusts the lower and upper bound of the homeostatic window down by apredetermined amount, e.g., 5% or 10%, of their previous values.Processor 210 may maintain the homeostatic window at this new positionuntil patient 112 performs a subsequent wrist flexion task. In someexamples, processor 210 continues to adjust the homeostatic window downuntil the input from sensors 109 indicates that the wrist flexion ofpatient 112 reaches the therapeutic magnitude determined by theclinician.

For example, processor 206, via telemetry module 208, may receive fromexternal programmer 104, information indicating feedback from a patient112 to adjust one or more bounds of the homeostatic window. For example,processor 206, via telemetry module 208, receives instructions to shiftdownward the upper bound of the homeostatic window, or the entirehomeostatic window itself. To drive the signal to a lower window,processor 206 increases the one or more parameters of the electricalstimulation therapy, and thereby increases the magnitude of electricalstimulation therapy to reduce the symptoms of the patient 112. Inanother example, processor 206, via telemetry module 208, receivesinstructions from external programmer 104 to shift upward the lowerbound of the homeostatic window, or the entire homeostatic windowitself. This has the effect of allowing the signal to float to a higherwindow, effectively causing the IMD 106 to decrease the one or moreparameters of the electrical stimulation therapy, and thereby decreasethe magnitude of electrical stimulation therapy to reduce side effects.While processor 206, in response to instructions from a patient 112, mayadjust one or more bounds of the homeostatic window, or the homeostaticwindow itself, typically, to ensure the safety of the patient, processor206 may not alter the therapeutic window that sets lower and upperbounds for the one or more parameters of the electrical stimulationtherapy without the authorization of a clinician.

In another example, processor 206 receives a signal from sensors 109indicative of a physiological parameter of the patient. In response tothe physiological parameter, processor 206 adjusts one or both bounds ofthe homeostatic window. For example, in response to signals from sensors109, processor 206 may determine that the magnitude of one or moreparameters defining the electrical stimulation therapy is insufficientto reduce the one or more symptoms of patient 112. In this example,processor 206 shifts downward the upper bound of the homeostatic window,or the entire homeostatic window itself. In another example, in responseto signals from sensors 109, processor 206 may determine that themagnitude of one or more parameters defining the electrical stimulationtherapy may result in one or more side effects in patient 112. In thisexample, processor 206 shifts upward the lower bound of the homeostaticwindow, or the entire homeostatic window itself. In further examples,processor 206 adjusts the lower bound of the homeostatic window, theupper bound of the homeostatic window, or the entire homeostatic windowitself. By allowing the signal to float at different magnitudes, thesystem 100 effectively adjusts the one or more parameters of theelectrical stimulation therapy, and thereby adjusts the magnitude ofelectrical stimulation therapy to compensate for different activitylevels of patient 112. Typically, processor 206 may not independentlyresize the therapeutic window beyond safety guidelines set by theclinician, which may be expressed as a maximum adjustment to upperbound, lower bound, or window shift, either in an absolute sense or inthe sense of a maximum adjustment per unit time.

As described above, in one example, for a proportional neurologicalsignal, such as a signal within the Beta frequency band, a cliniciansets the upper bound of the homeostatic window as the magnitude of thesensed signal while receiving a minimum magnitude of electricalstimulation therapy sufficient to reduce one or more symptoms of thedisease and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease. Alternatively, theclinician may set the upper bound of the homeostatic window as themagnitude of the sensed signal while receiving electrical stimulationtherapy and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease, wherein theelectrical stimulation is at a magnitude sufficient to reduce one ormore symptoms of the disease or disorder but which, above the magnitude,no further substantial reduction in the one or more symptoms isachieved.

Further, in one example, for a proportional neurological signal, such asa signal within the Beta frequency band, the clinician sets the lowerbound of the homeostatic window as a magnitude of the sensed signalwhile receiving a minimum magnitude of electrical stimulation therapysufficient to reduce one or more symptoms of a disease and while thepatient is receiving medication for reduction of one or more symptoms ofa disease or disorder. Alternatively, the clinician may set the upperbound of the homeostatic window as the magnitude of the sensed signalwhile receiving electrical stimulation therapy sufficient to causemaximum reduction of the one or more symptoms of the disease or disorderwithout inducing substantial side effects in the patient and while thepatient is not receiving the medication for reduction of the one or moresymptoms of the disease. Note that, for an inversely proportionalsignal, such as a signal within the Gamma frequency band, the processfor setting the upper and lower bounds is reversed.

By using the homeostatic window to heuristically define an upper boundand a lower bound as thresholds for adjusting the one or more parametersdefining the electrical stimulation, processor 206 ensures, via thelower and upper bounds of the homeostatic window, that the neurologicalsignal floats within a range of expected behavior, and only triggersadjustment to the one or more parameters defining the electricalstimulation when the neurological signal deviates from the expectedbehavior. It should be further noted that, while the lower and upperbounds are defined while the patient is either off medication or onmedication, after defining the homeostatic window, electricalstimulation therapy is delivered according to the homeostatic windowregardless of whether the patient is on or off medication.

Furthermore, the processor 206 ensures, via the lower bound of thetherapeutic window, that IMD 106 does not reduce the magnitude ofelectrical stimulation below a minimum magnitude that the cliniciandetermined should be continuously delivered to the patient.Additionally, processor 206 ensures, via the upper bound of thetherapeutic window, that IMD 106 does not increase the magnitude ofelectrical stimulation above a maximum magnitude that the cliniciandetermined is safe or comfortable for the patient. By permittingadaptive adjustment of one or more stimulation parameters, whileconstraining the values of the one or more parameters to reside within arange of values from the lower bound to the upper bound of thehomeostatic therapeutic window, processor 206 may promote therapeuticefficacy and/or power efficiency. Further, the system 100 may avoidcontinuously adjusting, throttling, or oscillating the one or morestimulation parameters, avoiding excessive power drain on the system 100without providing further treatment of the symptoms of the patient.

Thus, processor 210 may adjust the magnitude or magnitude of one or moreparameters defining the electrical stimulation therapy only when thesignal deviates from the homeostatic window to ensure that under normalconditions, the electrical stimulation remains constant, while stillretaining the ability to dynamically increase or decrease the electricalstimulation to adapt to the needs of the patient.

FIG. 3 is a block diagram of the external programmer 104 of FIG. 1 .Although programmer 104 may generally be described as a hand-helddevice, programmer 104 may be a larger portable device or a morestationary device. In addition, in other examples, programmer 104 may beincluded as part of an external charging device or include thefunctionality of an external charging device. As illustrated in FIG. 3 ,programmer 104 may include a processor 310, memory 311, user interface302, telemetry module 308, and power source 320. Memory 311 may storeinstructions that, when executed by processor 310, cause processor 310and external programmer 104 to provide the functionality ascribed toexternal programmer 104 throughout this disclosure. Each of thesecomponents, or modules, may include electrical circuitry that isconfigured to perform some or all of the functionality described herein.For example, processor 310 may include processing circuitry configuredto perform the processes discussed with respect to processor 310.

In general, programmer 104 comprises any suitable arrangement ofhardware, alone or in combination with software and/or firmware, toperform the techniques attributed to programmer 104, and processor 310,user interface 302, and telemetry module 308 of programmer 104. Invarious examples, programmer 104 may include one or more processors,which may include fixed function processing circuitry and/orprogrammable processing circuitry, as formed by, for example, one ormore microprocessors, DSPs, ASICs, FPGAs, or any other equivalentintegrated or discrete logic circuitry, as well as any combinations ofsuch components. Programmer 104 also, in various examples, may include amemory 311, such as RAM, ROM, PROM, EPROM, EEPROM, flash memory, a harddisk, a CD-ROM, comprising executable instructions for causing the oneor more processors to perform the actions attributed to them. Moreover,although processor 310 and telemetry module 308 are described asseparate modules, in some examples, processor 310 and telemetry module308 may be functionally integrated with one another. In some examples,processor 310 and telemetry module 308 correspond to individual hardwareunits, such as ASICs, DSPs, FPGAs, or other hardware units.

Memory 311 (e.g., a storage device) may store instructions that, whenexecuted by processor 310, cause processor 310 and programmer 104 toprovide the functionality ascribed to programmer 104 throughout thisdisclosure. For example, memory 311 may include instructions that causeprocessor 310 to obtain a parameter set from memory, select a spatialelectrode movement pattern, or receive a user input and send acorresponding command to IMD 104, or instructions for any otherfunctionality. In addition, memory 311 may include a plurality ofprograms, where each program includes a parameter set that definesstimulation therapy.

User interface 302 may include a button or keypad, lights, a speaker forvoice commands, a display, such as a liquid crystal (LCD),light-emitting diode (LED), or organic light-emitting diode (OLED). Insome examples the display may be a touch screen. User interface 302 maybe configured to display any information related to the delivery ofstimulation therapy, identified patient behaviors, sensed patientparameter values, patient behavior criteria, or any other suchinformation. User interface 302 may also receive user input via userinterface 302. The input may be, for example, in the form of pressing abutton on a keypad or selecting an icon from a touch screen.

Telemetry module 308 may support wireless communication between IMD 106and programmer 104 under the control of processor 310. Telemetry module308 may also be configured to communicate with another computing devicevia wireless communication techniques, or direct communication through awired connection. In some examples, telemetry module 308 provideswireless communication via an RF or proximal inductive medium. In someexamples, telemetry module 308 includes an antenna, which may take on avariety of forms, such as an internal or external antenna.

Examples of local wireless communication techniques that may be employedto facilitate communication between programmer 104 and IMD 106 includeRF communication according to the 802.11 or Bluetooth specification setsor other standard or proprietary telemetry protocols. In this manner,other external devices may be capable of communicating with programmer104 without needing to establish a secure wireless connection. Asdescribed herein, telemetry module 308 may be configured to transmit aspatial electrode movement pattern or other stimulation parameter valuesto IMD 106 for delivery of stimulation therapy.

According to the techniques of the disclosure, in some examples,processor 310 of external programmer 104 defines the parameters of ahomeostatic therapeutic window, stored in memory 311, for deliveringadaptive DBS to patient 112. In one example, processor 311 of externalprogrammer 104, via telemetry module 308, issues commands to IMD 106causing IMD 106 to deliver electrical stimulation therapy via electrodes116, 118 via leads 114.

In one example, the homeostatic window has an upper bound and a lowerbound that define an upper limit and a lower limit, respectively, forone or more parameters that define the electrical stimulation therapythat IMD 106 delivers to patient 112. For example, while the patient isnot taking medication selected to reduce one or more symptoms, aclinician, via user interface 302 of external programmer 104, instructsIMD 106, via telemetry module 308, to gradually increase one or moreparameters, such as a maximum voltage or current amplitude, defining theelectrical stimulation therapy delivered to patient 112 to determine thepoint at which further increase to the magnitude of one or moreparameters defining the electrical stimulation therapy results in theonset of side effects for the patient. The clinician, via user interface302 of external programmer 104, defines the lower bound of thehomeostatic window as a magnitude of the signal of the patient at thismagnitude of electrical stimulation.

Further, while the patient is on medication selected to reduce the oneor more symptoms, a clinician, via user interface 302 of externalprogrammer 104, instructs IMD 106, via telemetry module 308, togradually decrease the one or more parameters, such as a minimum voltageor current amplitude, defining the electrical stimulation therapydelivered to patient 112 to determine a minimum magnitude of the one ormore parameters sufficient to reduce or maintain reduction of one ormore symptoms without the symptoms breaking through or reemerging. Theclinician, via user interface 302 of external programmer 104, may definethis magnitude as a potential lower therapy limit for the device toadapt to when adaptive stimulation is running.

In another example, while the patient is off medication selected toreduce the one or more symptoms, sensors 109 measure the one or moresymptoms and relay, via telemetry module 308, the measurements toprocessor 310 of external programmer 104. Processor 310 instructs IMD106, via telemetry module 308, to gradually increase one or moreparameters, such as a minimum voltage or current amplitude, defining theelectrical stimulation therapy delivered to patient 112 to determine aminimum magnitude of the one or more parameters sufficient to reduce theone or more symptoms. Processor 310 defines the upper bound of thehomeostatic window as a magnitude of the signal of the patient at thismagnitude of electrical stimulation, and stores this value in memory311.

Further, while the patient is on medication selected to reduce the oneor more symptoms, sensors 109 measure the one or more symptoms andrelay, via telemetry module 308, the measurements to processor 310 ofexternal programmer 104. Processor 310 instructs IMD 106, via telemetrymodule 308, to gradually decrease the one or more parameters, such as aminimum voltage or current amplitude, defining the electricalstimulation therapy delivered to patient 112 to determine a minimummagnitude of the one or more parameters sufficient to reduce or maintainreduction of one or more symptoms without the symptoms breaking throughor reemerging. Processor 310 defines the lower bound of the homeostaticwindow as a magnitude of the signal of the patient at this magnitude ofelectrical stimulation, and stores this value in memory 311.

Additionally, in one example, patient 112, via user interface 302,provides feedback to processor 310 indicating the efficacy of theelectrical stimulation therapy. In response to the feedback, processor310 adjusts one or more bounds of the homeostatic window. For example,if patient 112 determines that the electrical stimulation therapy is nottreating the one or more symptoms of patient 112, patient 112 mayprovide feedback to external programmer 104 via user interface 302 toincrease the electrical stimulation therapy. For example, if patient 112determines that the electrical stimulation therapy is not treating theone or more symptoms of patient 112 effectively, patient 112 may providefeedback, via user interface 302, to processor 310, causing processor310 to shift downward the upper bound of the homeostatic window, or theentire homeostatic window itself. To drive the sensed signal to a lowerwindow, the processor 310 issues instructions, via telemetry module 308,to IMD 106 to increase the one or more parameters of the electricalstimulation therapy, and thereby increases the magnitude of electricalstimulation therapy to reduce the symptoms of the patient. In anotherexample, if patient 112 determines that the electrical stimulationtherapy is unpleasant, causes side effects, or is otherwiseuncomfortable to patient 112, patient 112 may provide feedback, via userinterface 302, to processor 310 causing processor 310 to shift upwardthe lower bound of the homeostatic window, or the entire homeostaticwindow itself. This has the effect of allowing the signal to float to ahigher window, effectively causing IMD 106 to decrease the one or moreparameters of the electrical stimulation therapy, and thereby decreasesthe magnitude of electrical stimulation therapy to reduce side effects.While the patient 112 may adjust one or more bounds of the homeostaticwindow, or the homeostatic window itself, typically, to ensure thesafety of the patient, the patient 112 may not alter the therapeuticwindow that sets lower and upper bounds for the one or more parametersof the electrical stimulation therapy.

In another example, processor 310 receives, via telemetry module 308, asignal from sensors 109 indicative of a physiological parameter of thepatient. In response to the physiological parameter, processor 310 ofexternal programmer 104 issues instructions to IMD 106 to adjust one orboth bounds of the homeostatic window. For example, in response tosignals from sensors 109, processor 310 may determine that the magnitudeof one or more parameters defining the electrical stimulation therapy isinsufficient to reduce the one or more symptoms of patient 112. In thisexample, processor 310, via telemetry module 308, issues instructions toIMD 106 to shift downward the upper bound of the homeostatic window, orthe entire homeostatic window itself. To drive the signal to a lowerwindow, the IMD 106 effectively increases the one or more parameters ofthe electrical stimulation therapy, and thereby increases the magnitudeof electrical stimulation therapy to reduce the symptoms of the patient.In another example, in response to signals from sensors 109, processor310 may determine that, based on a symptom of the patient (e.g., tremor,rigidity, or wrist flexion), a posture of the patient (e.g., laying,sitting, standing, etc.) or an activity level of the patient (i.e.,sleeping, walking, exercising, etc.), processor 310 should adjust themagnitude of one or more parameters defining the electrical stimulationtherapy. Processor 310 may issue instructions, via telemetry module 308,to IMD 106 to adjust the lower bound of the homeostatic window, theupper bound of the homeostatic window, or the entire homeostatic windowitself. By allowing the signal to float at different magnitudes, IMD 106adjusts the one or more parameters of the electrical stimulationtherapy, and thereby adjusts the magnitude of electrical stimulationtherapy to compensate for different activity levels of patient 112.Typically, processor 310 may not resize the therapeutic window beyondsafety guidelines set by the clinician, which may be expressed as amaximum adjustment to upper bound, lower bound, or window shift, eitherin an absolute sense or in the sense of a maximum adjustment per unittime.

FIG. 4 is a timing diagram illustrating the example system of FIG. 1 forsetting a lower bound 414 and an upper bound 412 of the homeostaticwindow 410 for a proportional signal according to the techniques of thedisclosure. In the example of FIG. 4 , the horizontal axis depicts timeand is identical for both graphs 400 and 401. The vertical axis of graph400 depicts the magnitude of the one or more parameters of theelectrical stimulation, while the vertical axis of graph 401 depicts themagnitude of the sensed neurological signal.

In the example of FIG. 4 , IMD 106, via one or more electrodes, monitorsa signal 402, e.g., a neurological signal within a Beta frequency bandof brain 120 of patient 112, that is proportional to the severity of oneor more symptoms of the patient. Further, IMD 106 delivers electricalstimulation therapy having a voltage magnitude 404 within an upper limit422 and a lower limit 424 of therapeutic window 420. Graph 400 depicts avoltage amplitude of electrical stimulation delivered to patient 112along the y-axis with respect to time along the x-axis. Graph 401depicts a magnitude of a signal, such as a neurological signal withinthe Beta frequency band, of patient 112 along the y-axis with respect totime along the x-axis. Graph 400 depicts the electrical stimulationprovided by IMD 106 in response to the measured signal of graph 401.

In the example of FIG. 4 , a patient 112 has taken medication selectedto reduce one or more symptoms. For Parkinson's disease, suchmedications may include extended release forms of dopamine agonists,regular forms of dopamine agonists, controlled release forms ofcarbidopa/levodopa (CD/LD), regular forms of CD/LD, entacapone,rasagiline, selegiline, and amantadine.

To determine the lower bound 414 of homeostatic window 410, in oneexample, a clinician ensures that the patient has received one ofmedication selected to reduce one or more symptoms. Typically, theclinician ensures that the patient has been on the medication, i.e., hasbeen taking regularly prescribed doses of the medication, for at leastapproximately 72 hours for extended release forms of dopamine agonists,the patient has been on medication for at least approximately 24 hoursfor regular forms of dopamine agonists and controlled release forms ofCD/LD, and the patient has been on medication for at least approximately12 hours for regular forms of CD/LD, entacapone, rasagiline, selegiline,and amantadine. In FIG. 4 , the effectiveness of the medicine may beobserved as, for example, a decrease 406 in a Beta signal of a brain ofthe patient. In other examples, instead of, or complimentary with themedication selected to reduce the one or more symptoms, the patient 112receives a maximum magnitude of electrical stimulation therapy, asdefined by the upper bound of the therapeutic window for patient safetyand/or comfort, to reduce the one or more symptoms.

The clinician, via external programmer 104, instructs IMD 106 to titratethe voltage amplitude 404 of the electrical stimulation therapydelivered to patient 112. Typically, the clinician will begin at a valuefor the voltage amplitude 404 approximately in the middle of thetherapeutic window and instruct IMD 106 to gradually decrease themagnitude of the voltage amplitude 404. However, in some examples, theclinician begins at a value for the voltage amplitude 404 approximatelyequal to the upper bound of the therapeutic window and graduallydecreases the magnitude of the voltage amplitude. The cliniciandetermines the point at which the magnitude of the voltage amplitude 404is sufficient enough to reduce the one or more symptoms of patient 112,and any further reduction in the one or more parameters causes symptomsof the disease of patient 112 to emerge. In the example of Parkinson'sdisease, the clinician determines the point at which further reductionin the voltage amplitude 404 causes an increase in the severity of thesymptoms of patient 112 under the UPDRS or MDS-UPDRS.

At this magnitude of the voltage amplitude 404, the clinician measuresthe magnitude of the signal 402 of the patient 112 and sets, viaexternal programmer 104, this magnitude as the lower bound 414 of thehomeostatic window 410. In some examples, the clinician may select avalue for the lower bound 414 of the homeostatic window to be apredetermined amount, e.g., 5% or 10%, lower than the magnitude at whichthe symptoms of the patient 112 emerge to prevent emergence of thesymptoms of the patient 112 during subsequent use.

In another example, the clinician sets the lower bound by first ensuringthat the patient is off medication for the one or more symptoms.Typically, the clinician ensures that, prior to the time at which thelower bound is determined, the patient has been off the medication,i.e., has not taken the medication, for at least approximately 72 hoursfor extended release forms of dopamine agonists, the patient has beenoff medication for at least approximately 24 hours for regular forms ofdopamine agonists and controlled release forms of CD/LD, and the patienthas been off medication for at least approximately 12 hours for regularforms of CD/LD, entacapone, rasagiline, selegiline, and amantadine.

In this example, the clinician delivers electrical stimulation having avalue for the voltage amplitude 404 approximately equal to the upperbound of the therapeutic window. In some examples, the cliniciandelivers electrical stimulation having a value for the voltage amplitudeslightly below the magnitude which induces side effects in the patient112. Typically, this causes maximal reduction of the one or moresymptoms of the disease of the patient 112, and therefore maximalreduction of the signal. At this magnitude of the voltage amplitude 404,the clinician measures the magnitude of the signal 402 of the patient112 and sets, via external programmer 104, this magnitude as the lowerbound 414 of the homeostatic window 410. In some examples, the clinicianmay select a value for the lower bound 414 of the homeostatic windowthat is a predetermined amount, e.g., 5% or 10%, lower than themagnitude at which the symptoms of the patient 112 emerge to preventemergence of the symptoms of the patient 112 during subsequent use.

To determine the upper bound 412 of homeostatic window 410, theclinician ensures that the patient has not received medication selectedto reduce the one or more symptoms. Typically, to set the upper bound ofthe homeostatic window, the clinician ensures that the patient has beenoff medication, i.e., has not taken the medication, for at leastapproximately 72 hours for extended release forms of dopamine agonists,the patient has been off medication for at least approximately 24 hoursfor regular forms of dopamine agonists and controlled release forms ofCD/LD, and the patient has been off medication for at leastapproximately 12 hours for regular forms of CD/LD, entacapone,rasagiline, selegiline, and amantadine.

The clinician, via external programmer 104, instructs IMD 106 to titratethe voltage amplitude 404 of the electrical stimulation therapydelivered to patient 112. Typically, the clinician will begin with avery low value for the voltage amplitude 404 and instruct IMD 106 togradually increase the magnitude of the voltage amplitude 404. In oneexample, the clinician determines a minimum magnitude of the voltageamplitude 404 sufficient to reduce the one or more symptoms of patient112. In another example, the clinician determines the point at whichfurther increase to the magnitude of the voltage amplitude 404 definingthe electrical stimulation therapy does not cause a further reduction inthe severity of the symptoms of the disease of patient 112. For example,in the example of Parkinson's disease, the clinician may determine thepoint at which increasing the magnitude of the voltage amplitude 404does not cause a further reduction in the score of patient 112 under theUPDRS or MDS-UPDRS. At this magnitude of the voltage amplitude 404 ofthe electrical stimulation therapy, the clinician measures the magnitudeof the signal 402 of the patient 112 and sets, via external programmer104, this magnitude as the upper bound 412 of the homeostatic window410. In some examples, the clinician may select a value for the upperbound 412 of the homeostatic window that is a predetermined amount,e.g., 5% or 10%, higher than measured magnitude of the signal toprevent, during subsequent use, discomfort to patient 112 due to sideeffects of the therapy.

In the example of FIG. 4 , during time 430, the sensed signal (e.g., thesensed neurological signal or physiological parameter of patient 112) isbelow the lower bound 414 of the homeostatic window. Accordingly, IMD106 decrements the voltage amplitude of the electrical stimulation. Notethat IMD 106 does not decrement stimulation below the lower bound 424 ofthe therapeutic window. Similarly, during time 432, the signal is abovethe upper bound 412 of the homeostatic window. Accordingly, IMD 106increments the voltage amplitude of the electrical stimulation. Notethat IMD 106 does not increment stim above the upper bound 422 of thetherapeutic window. When the signal returns to within the homeostaticwindow at time 434, IMD maintains the present voltage amplitude of theelectrical stimulation.

FIG. 5 is a graph illustrating an example operation for setting a lowerbound of the homeostatic window according to the techniques of thedisclosure. In the example of FIG. 5 , IMD 106, via one or moreelectrodes, monitors a signal, e.g., a neurological signal within theBeta frequency band of brain 120 of patient 112, that is proportional tothe severity of one or more symptoms of the patient. Further, IMD 106delivers electrical stimulation therapy having a voltage magnitude 404within an upper limit and a lower limit of a therapeutic window. Sensors109 monitor a physiological parameter of patient 112. In the example ofFIG. 5 , sensors 109 are accelerometers that monitor a magnitude 504 ofa tremor of patient 112. FIG. 5 depicts the output signal 504 of sensors109 and the voltage magnitude 404 along the y-axis with respect to timein seconds along the x-axis.

To determine the lower bound 414 of homeostatic window 410, a clinicianensures that, the patient has received medication selected to reduce oneor more symptoms. Typically, the clinician ensures that, prior to thetime that the lower bound is defined, the patient has been on themedication, i.e., has been taking regularly prescribed doses of themedication, for at least approximately 72 hours for extended releaseforms of dopamine agonists, the patient has been on medication for atleast approximately 24 hours for regular forms of dopamine agonists andcontrolled release forms of CD/LD, and the patient has been onmedication for at least approximately 12 hours for regular forms ofCD/LD, entacapone, rasagiline, selegiline, and amantadine.

The clinician, via external programmer 104, instructs IMD 106 to titratethe voltage amplitude 404 of the electrical stimulation therapydelivered to patient 112. Typically, the clinician will begin at amidrange value for the voltage amplitude 404 and instruct IMD 106 togradually decrease the magnitude of the voltage amplitude 404. Theclinician determines the point at which the magnitude of the voltageamplitude 404 is sufficient enough to reduce the one or more symptoms ofpatient 112, and any further reduction in the one or more parameterscauses symptoms of the disease of patient 112 to emerge. In the exampleof FIG. 5 , external processor ramps down voltage amplitude 404 of theelectrical stimulation therapy until patient 112 experiences one or more“break-through” events 502A-502B of the tremor of patient 112, i.e.,failure to reduce symptoms or return of symptoms.

At this magnitude of the voltage amplitude 404 that the “break-through”events 502A-502B occur, the clinician measures the magnitude of thesignal of the patient 112 and sets, via external programmer 104, thismagnitude as the lower bound 414 of the homeostatic window. In someexamples, the clinician may select a value for the lower bound of thehomeostatic window that is a predetermined amount, e.g., 5% or 10%,lower than the magnitude at which the symptoms of the patient 112 emergeto prevent additional “break-through” events from occurring duringsubsequent use. In addition, a clinician may use the magnitude of thevoltage amplitude 404 found in this test to set the lower bound 424 ofthe therapeutic window. In other words, the clinician may set thismagnitude as the minimum amplitude to which the system 100 may reducethe electrical stimulation voltage so as to prevent any symptombreakthrough.

FIG. 6 is a timing diagram illustrating the example system of FIG. 1 forsetting a lower bound and an upper bound of the homeostatic window foran inversely proportional signal according to the techniques of thedisclosure. In the example of FIG. 6 , the horizontal axis depicts timeand is identical for both graphs 600 and 601. The vertical axis of graph600 depicts the magnitude of the one or more parameters of theelectrical stimulation, while the vertical axis of graph 401 depicts themagnitude of the sensed neurological signal.

In the example of FIG. 6 , IMD 106, via one or more electrodes, monitorsa biological signal 602, e.g., a neurological signal within the Gammafrequency band of brain 120 of patient 112, that is inverselyproportional to the severity of side effects due to electricalstimulation therapy. Further, IMD 106 delivers electrical stimulationtherapy having a voltage magnitude 404 within an upper limit 422 and alower limit 424 of therapeutic window 420. Graph 600 depicts a voltageamplitude of electrical stimulation delivered to patient 112 along they-axis with respect to time along the x-axis. Graph 601 depicts amagnitude of a signal, such as a signal within the Gamma frequency band,of patient 112 along the y-axis with respect to time along the x-axis.Graph 600 depicts the electrical stimulation provided by IMD 106 inresponse to the measured signal of graph 601.

Note that in contrast to FIG. 4 , FIG. 6 depicts a signal that isinversely proportional to the severity of side effects due to electricalstimulation therapy. In other words, as the magnitude of the severity ofthe side effects due to electrical stimulation therapy increases, themagnitude of the inversely proportional signal decreases. Accordingly,the upper and lower bounds for the inversely proportional signal are theopposite of the upper and lower bounds of the proportional signal ofFIG. 4 .

In the example of FIG. 6 , a patient 112 has not taken medicationselected to reduce one or more symptoms prior to the evaluation, asdescribed above. For Parkinson's disease, such medications includeextended release forms of dopamine agonists, regular forms of dopamineagonists, controlled release forms of carbidopa/levodopa (CD/LD),regular forms of CD/LD, entacapone, rasagiline, selegiline, andamantadine.

To determine the upper bound 412 of homeostatic window 410, a clinicianensures that the patient has received medication selected to reduce oneor more symptoms. Typically, the clinician ensures that, prior todefining the upper bound, the patient has been on the medication, i.e.,has been taking regularly prescribed doses of the medication, for atleast approximately 72 hours for extended release forms of dopamineagonists, the patient has been on medication for at least approximately24 hours for regular forms of dopamine agonists and controlled releaseforms of CD/LD, and the patient has been on medication for at leastapproximately 12 hours for regular forms of CD/LD, entacapone,rasagiline, selegiline, and amantadine. In FIG. 6 , the effectiveness ofthe medicine may be observed as an increase 602 in the neurologicalsignal within the Gamma frequency band.

The clinician, via external programmer 104, instructs 1 MB 106 totitrate the voltage amplitude 404 of the electrical stimulation therapydelivered to patient 112. Typically, the clinician will begin at amidrange value for the voltage amplitude 404 and instruct IMD 106 togradually decrease the magnitude of the voltage amplitude 404. Theclinician determines the point at which the magnitude of the voltageamplitude 404 is sufficient enough to reduce the one or more symptoms ofpatient 112, and any further reduction in the one or more parameterscauses symptoms of the disease of patient 112 to emerge. In the exampleof Parkinson's disease, the clinician determines the point at whichfurther reduction in the voltage amplitude 404 causes an increase in theseverity of the symptoms of patient 112 under the UPDRS or MDS-UPDRS.

At this magnitude of the voltage amplitude 404, the clinician measuresthe magnitude of the signal 402 of the patient 112 and sets, viaexternal programmer 104, this magnitude of the signal as the upper bound412 of the homeostatic window 410. In some examples, the clinician mayselect a value for the upper bound 412 of the homeostatic window that isa predetermined amount, e.g., 5% or 10%, lower than the magnitude atwhich the symptoms of the patient 112 emerge to prevent emergence of thesymptoms of the patient 112 during subsequent use.

To determine the upper bound 412 of homeostatic window 410, theclinician ensures that the patient has received medication selected toreduce the one or more symptoms. Typically, when medication andelectrical stimulation are combined, a Gamma signal is selected as thesensed signal for defining homeostatic window 410, as opposed a Betasignal. Thus, to set the upper bound of the homeostatic window for asystem monitoring a signal within the Gamma frequency band of brain 120of patient 112, typically the clinician ensures that, prior to definingthe upper bound 412, the patient has been on medication, i.e., has beentaking regularly prescribed doses of the medication, for at leastapproximately 72 hours for extended release forms of dopamine agonists,the patient has been on medication for at least approximately 24 hoursfor regular forms of dopamine agonists and controlled release forms ofCD/LD, and the patient has been on medication for at least approximately12 hours for regular forms of CD/LD, entacapone, rasagiline, selegiline,and amantadine.

The clinician, via external programmer 104, instructs IMD 106 to titratethe voltage amplitude 404 of the electrical stimulation therapydelivered to patient 112. Typically, the clinician will begin with avery low value for the voltage amplitude 404 and instruct IMD 106 togradually increase the magnitude of the voltage amplitude 404. In oneexample, the clinician determines a minimum magnitude of the voltageamplitude 404 sufficient to reduce the one or more symptoms of patient112. In another example, the clinician determines the point at whichfurther increase to the magnitude of the voltage amplitude 404 of thedefining the electrical stimulation therapy causes side effect symptomsof the disease of patient 112. For example, in the example ofParkinson's disease, the clinician may determine the point at whichincreasing the magnitude of the voltage amplitude 404 causes the sideeffect dyskinesia.

At this magnitude of the voltage amplitude 404 of the electricalstimulation therapy, the clinician measures the magnitude of the signal602 of the patient 112 and sets, via external programmer 104, thismagnitude as the upper bound 412 of the homeostatic window 410. In someexamples, the clinician may select a value for the upper bound 412 ofthe homeostatic window that is a predetermined amount, e.g., 5% or 10%,lower than a measured magnitude of the signal to prevent, duringsubsequent use, discomfort to patient 112 due to side effects of thetherapy.

In the example of FIG. 6 , during time 630, the signal is below thelower bound 414 of the homeostatic window. Accordingly, IMD 106increments the voltage amplitude of the electrical stimulation. Notethat IMD 106 does not increment stim above the upper bound 422 of thetherapeutic window. Similarly, during time 632, the signal is above theupper bound 412 of the homeostatic window. Accordingly, IMD 106decrements the voltage amplitude of the electrical stimulation. Notethat IMD 106 does not decrement stim below the lower bound 424 of thetherapeutic window. When the signal returns to within the homeostaticwindow at time 434, IMD maintains the present voltage amplitude of theelectrical stimulation.

FIG. 7 is a flowchart illustrating an example operation for setting alower bound of the homeostatic window for a proportional signal, e.g., aneurological signal within the Beta frequency band, according to thetechniques of the disclosure. For convenience, FIG. 7 is described withreference to system 100 of FIG. 1 .

A clinician ensures that the patient has received medication selected toreduce one or more symptoms for at least time period prior to theevaluation as described above (702). Such medications include extendedrelease forms of dopamine agonists, regular forms of dopamine agonists,controlled release forms of carbidopa/levodopa (CD/LD), regular forms ofCD/LD, entacapone, rasagiline, selegiline, and amantadine. Typically, toset the lower bound of the homeostatic window, the clinician ensuresthat the patient has been on medication, i.e., has taken prescribeddoses of the medication, for at least approximately 72 hours forextended release forms of dopamine agonists, the patient has been onmedication for at least approximately 24 hours for regular forms ofdopamine agonists and controlled release forms of CD/LD, and the patienthas been on medication for at least approximately 12 hours for regularforms of CD/LD, entacapone, rasagiline, selegiline, and amantadine.

The clinician, via external programmer 104, instructs IMD 106 to titratedownward one or more parameters, such as a voltage or current amplitude,defining the electrical stimulation therapy delivered to patient 112(704). Typically, the clinician begins with a value in the middle of thetherapeutic window or near the upper bound of the therapeutic window forthe one or more parameters and instructs IMD 106 to gradually decreasethe magnitude of the one or more parameters. In one example, theclinician determines a minimum magnitude of the one or more parameterssufficient to prevent breakthrough of the one or more symptoms ofpatient 112 (706). For example, in the example of Parkinson's disease,the clinician determines the point at which the symptoms of Parkinson'sdisease in patient 112 emerge, as measured by sudden increase withrespect to tremor or rigidity, in the score of patient 112 under theUPDRS or MDS-UPDRS. In another example, the clinician measures a wristflexion of the patient and determines the point at which furtherdecrease to the magnitude of one or more parameters defining theelectrical stimulation therapy causes a sudden increase in the lack ofwrist flexion of the patient.

At this magnitude of one or more parameters defining the electricalstimulation therapy, the clinician measures the magnitude of the signalof the patient 112 (e.g., a signal within the Beta frequency band) (708)and sets, via external programmer 104, this magnitude as the lower boundof the homeostatic window (710). In some examples, the signal is aneurological signal within the Beta frequency band of the patient. Insome examples, the clinician may select a value for the lower bound ofthe homeostatic window that is a predetermined amount, e.g., 5% or 10%,higher than the measured magnitude of the signal to prevent breakthroughof the symptoms of patient 112.

However, in alternate examples, the clinician sets the lower bound byfirst ensuring that the patient is off medication for the one or moresymptoms. In this example, the clinician delivers electrical stimulationhaving a value for the one or more parameters approximately equal to theupper bound of the therapeutic window. In some examples, the cliniciandelivers electrical stimulation having a value for the one or moreparameters slightly below the magnitude which induces side effects inthe patient 112. Typically, this causes maximal reduction of the one ormore symptoms of the disease of the patient 112, and therefore maximalreduction of the signal. At this magnitude of the one or moreparameters, the clinician measures the magnitude of the signal of thepatient 112 and sets, via external programmer 104, this magnitude as thelower bound of the homeostatic window. In some examples, the clinicianmay select a value for the lower bound of the homeostatic window that isa predetermined amount, e.g., 5% or 10%, lower than the magnitude atwhich the symptoms of the patient 112 emerge to prevent emergence of thesymptoms of the patient 112 during subsequent use.

FIG. 8 is a flowchart illustrating an example operation for setting anupper bound of the homeostatic window for a proportional signalaccording to the techniques of the disclosure. For convenience, FIG. 8is described with reference to system 100 of FIG. 1 . In some examples,the proportional signal is a neurological signal within the Betafrequency band of brain 120 of patient 112.

A clinician ensures that the patient has not received medicationselected to reduce one or more symptoms (802). Such medications includeextended release forms of dopamine agonists, regular forms of dopamineagonists, controlled release forms of carbidopa/levodopa (CD/LD),regular forms of CD/LD, entacapone, rasagiline, selegiline, andamantadine. Typically, to set the upper bound of the homeostatic window,the clinician ensures that, prior to setting the upper bound of thehomeostatic window, the patient has not been on medication, i.e., hasnot taken the medication, for at least approximately 72 hours forextended release forms of dopamine agonists, the patient has not been onmedication for at least approximately 24 hours for regular forms ofdopamine agonists and controlled release forms of CD/LD, and the patienthas not been on medication for at least approximately 12 hours forregular forms of CD/LD, entacapone, rasagiline, selegiline, andamantadine.

The clinician, via external programmer 104, instructs IMD 106 to titrateupward one or more parameters, such as a minimum voltage or currentamplitude, defining the electrical stimulation therapy delivered topatient 112 (804). Typically, the clinician will begin at a midrangevalue for the one or more parameters and instruct IMD 106 to graduallyincrease the magnitude of the one or more parameters. The cliniciandetermines the point at which the magnitude of the one or moreparameters is sufficient enough to reduce the one or more symptoms ofpatient 112 (806). In some examples, the clinician determines the pointat which any further increase in the one or more parameters does notcause a further reduction in the symptoms of the disease of patient 112.In the example of Parkinson's disease, the clinician determines thepoint at which further increase in the one or more parameters does notcause a further reduction in the severity of the symptoms of patient 112under the UPDRS or MDS-UPDRS.

At this magnitude of one or more parameters defining the electricalstimulation therapy, the clinician measures the magnitude of the signalof the patient 112 (808) and sets, via external programmer 104, thismagnitude as the upper bound of the homeostatic window (810). In someexamples, the signal is a neurological signal within the Beta frequencyband of the patient. In some examples, the clinician may select a valuefor the upper bound of the homeostatic window that is a predeterminedamount, e.g., 5% or 10%, lower than the magnitude at which the symptomsof the patient 112 emerge to prevent emergence of the symptoms of thepatient 112 during subsequent use.

FIG. 9 is a flowchart illustrating an example operation for setting anupper bound of the homeostatic window for an inversely proportionalsignal, e.g., a signal within the Gamma frequency band, according to thetechniques of the disclosure. For convenience, FIG. 9 is described withreference to system 100 of FIG. 1 .

A clinician ensures that the patient has received medication selected toreduce one or more symptoms (902). Such medications include extendedrelease forms of dopamine agonists, regular forms of dopamine agonists,controlled release forms of carbidopa/levodopa (CD/LD), regular forms ofCD/LD, entacapone, rasagiline, selegiline, and amantadine. Typically, toset the upper bound of the homeostatic window, the clinician ensuresthat, prior to setting the upper bound of the homeostatic window, thepatient has been on medication, i.e., has been taking regularlyprescribed doses of the medication, for at least approximately 72 hoursfor extended release forms of dopamine agonists, the patient has been onmedication for at least approximately 24 hours for regular forms ofdopamine agonists and controlled release forms of CD/LD, and the patienthas been off medication for at least approximately 12 hours for regularforms of CD/LD, entacapone, rasagiline, selegiline, and amantadine.

The clinician, via external programmer 104, instructs IMD 106 to titratedownward one or more parameters, such as a voltage or current amplitude,defining the electrical stimulation therapy delivered to patient 112(904). Typically, the clinician begins with a value in the middle of thetherapeutic window or near the upper bound of the therapeutic window forthe one or more parameters and instructs IMD 106 to gradually decreasethe magnitude of the one or more parameters. In one example, theclinician determines a minimum magnitude of the one or more parameterssufficient to prevent breakthrough of the one or more symptoms ofpatient 112 (906). For example, in the example of Parkinson's disease,the clinician determines the point at which the symptoms of Parkinson'sdisease in patient 112 emerge, as measured by sudden increase withrespect to tremor or rigidity, in the score of patient 112 under theUPDRS or MDS-UPDRS. In another example, the clinician measures a wristflexion of the patient and determines the point at which furtherdecrease to the magnitude of one or more parameters defining theelectrical stimulation therapy causes a sudden increase in the lack ofwrist flexion of the patient.

At this magnitude of one or more parameters defining the electricalstimulation therapy, the clinician measures the magnitude of the signalof the patient 112 (908) and sets, via external programmer 104, thismagnitude as the upper bound of the homeostatic window (910). In someexamples, the signal is a neurological signal within the Gamma frequencyband of the patient. In some examples, the clinician may select a valuefor the upper bound of the homeostatic window that is a predeterminedamount, e.g., 5% or 10%, lower than measured magnitude of the signal toprevent, during subsequent use, discomfort to patient 112 due to sideeffects of the therapy.

However, in alternate examples, the clinician sets the upper bound byfirst ensuring that the patient is off medication for the one or moresymptoms. In this example, the clinician delivers electrical stimulationhaving a value for the one or more parameters approximately equal to theupper bound of the therapeutic window. In some examples, the cliniciandelivers electrical stimulation having a value for the one or moreparameters slightly below the magnitude which induces side effects inthe patient 112. Typically, this causes maximal reduction of the one ormore symptoms of the disease of the patient 112, and therefore maximalreduction of the signal. At this magnitude of the one or moreparameters, the clinician measures the magnitude of the signal of thepatient 112 and sets, via external programmer 104, this magnitude as theupper bound of the homeostatic window. In some examples, the clinicianmay select a value for the upper bound of the homeostatic window that isa predetermined amount, e.g., 5% or 10%, lower than the magnitude atwhich the symptoms of the patient 112 emerge to prevent emergence of thesymptoms of the patient 112 during subsequent use.

FIG. 10 is a flowchart illustrating an example operation for setting alower bound of the homeostatic window for an inversely proportionalsignal according to the techniques of the disclosure. For convenience,FIG. 10 is described with reference to system 100 of FIG. 1 .

A clinician ensures that the patient has not received medicationselected to reduce one or more symptoms prior to the evaluation (1002).Such medications include extended release forms of dopamine agonists,regular forms of dopamine agonists, controlled release forms ofcarbidopa/levodopa (CD/LD), regular forms of CD/LD, entacapone,rasagiline, selegiline, and amantadine. Typically, to set the lowerbound of the homeostatic window, the clinician ensures that the patienthas been on medication, i.e., has been taking regularly prescribed dosesof the medication, for at least approximately 72 hours for extendedrelease forms of dopamine agonists, the patient has been on medicationfor at least approximately 24 hours for regular forms of dopamineagonists and controlled release forms of CD/LD, and the patient has beenon medication for at least approximately 12 hours for regular forms ofCD/LD, entacapone, rasagiline, selegiline, and amantadine.

The clinician, via external programmer 104, instructs IMD 106 to titrateupward one or more parameters, such as a minimum voltage or currentamplitude, defining the electrical stimulation therapy delivered topatient 112 (1004). Typically, the clinician will begin at a midrangevalue for the one or more parameters and instruct IMD 106 to graduallyincrease the magnitude of the one or more parameters. The cliniciandetermines the point at which the magnitude of the one or moreparameters is sufficient enough to reduce the one or more symptoms ofpatient 112 (1006). In some examples, the clinician determines the pointat which any further increase in the one or more parameters does notcause a further reduction in the symptoms of the disease of patient 112.In the example of Parkinson's disease, the clinician determines thepoint at which further increase in the one or more parameters does notcause a further reduction in the severity of the symptoms of patient 112under the UPDRS or MDS-UPDRS.

At this magnitude of one or more parameters defining the electricalstimulation therapy, the clinician measures the magnitude of the signalof the patient 112 (1008) and sets, via external programmer 104, thismagnitude as the lower bound of the homeostatic window (810). In someexamples, the signal is a neurological signal within the Gamma frequencyband of the patient. In some examples, the clinician may select a valuefor the lower bound of the homeostatic window that is a predeterminedamount, e.g., 5% or 10%, lower than the magnitude at which the symptomsof the patient 112 emerge to prevent emergence of the symptoms of thepatient 112 during subsequent use.

FIG. 11 is a flowchart illustrating an example operation for deliveringadaptive DBS based on the deviation of a signal from the homeostaticwindow according to the techniques of the disclosure. For convenience,FIG. 11 is described with respect to FIG. 1 and further with respect toa proportional signal, such as a neurological signal within the Betafrequency band of brain 120 of patient 112.

System 100 may adaptively deliver electrical stimulation and adjust oneor more parameters defining the electrical stimulation within aparameter range defined by the lower and upper bounds of the therapeuticwindow based on the activity of the sensed signal within the homeostaticwindow. For example, IMD 106, via electrodes 116, 118, senses a signalof the brain 120 of patient 112 (1102). In some examples, this signal isa neurological signal within the Beta frequency band of the brain 120 oranother proportional signal.

IMD 106 determines whether the sensed signal of patient 112 is greaterthan an upper bound of the homeostatic window (1104). Upon determiningthat the signal of patient 112 is greater than an upper bound of thehomeostatic window, IMD 106 increases the magnitude of one or moreparameters defining the electrical stimulation (1110). Note that if thesensed signal were instead an inversely proportional signal such as aneurological signal within the Gamma frequency band, the electricalstimulation magnitude would instead be decreased. Typically, IMD 106increases the magnitude of one or more parameters such that theelectrical stimulation is increased at a maximum ramp rate defined bythe clinician.

If IMD 106 determines that the sensed signal of patient 112 is notgreater than the upper bound of the homeostatic window, IMD 106determines whether the sensed signal of patient 112 is less than a lowerbound of the homeostatic window (1106). Upon determining that the signalof patient 112 is less than a lower bound of the homeostatic window, IMD106 decreases the magnitude of one or more parameters defining theelectrical stimulation (1112). Typically, IMD 106 decreases themagnitude of one or more parameters such that the electrical stimulationis decreased at a maximum ramp rate defined by the clinician.

Note that, as described above, the signal is proportional to theseverity of the one or more symptoms of the patient (for example, as isthe case when monitoring neurological signals within the Beta frequencyband of the brain of patient 112). Thus, for a proportional signal suchas beta, IMD 106 increases the magnitude of one or more parameters ofthe electrical stimulation when the signal is greater than the upperbound and decreases the magnitude of one or more parameters of theelectrical stimulation when the signal is less than the lower bound.However, where the signal is inversely proportional to the severity ofthe one or more symptoms of the patient (for example, as is the casewhen monitoring a neurological signal within the Gamma frequency band ofthe brain of patient 112), IMD 106 operates in an opposite manner.Accordingly, for an inversely proportional signal such as gamma, IMD 106increases the magnitude of one or more parameters of the electricalstimulation when the signal is less than the lower bound and decreasesthe magnitude of one or more parameters of the electrical stimulationwhen the signal is greater than the upper bound.

As described above, the maximum ramp rate is typically determined basedon a factor of the tolerance of the patient and the capabilities ofsystem 100. In some examples, the maximum ramp rate is at leastapproximately 0.1 Volts per 400 milliseconds. In some examples, theclinician titrates a plurality of ramps, such as 0.1 Volts per 400milliseconds; 0.5 Volts per 400 milliseconds; 1 Volt per 400milliseconds; and 2 Volts per 400 milliseconds, and selects a maximumramp rate based on the tolerance of the patient and the reliability ofthe system 100. Typically, IMD 106 incrementally adjusts the magnitudeof the one or more parameters. For example, IMD 106 may incrementallyincrease or decrease the magnitude of the one or more parameters by apartial amount such that, by repeating the operation of FIG. 8 at aparticular frequency, IMD 106 effectively adjusts the magnitude of theone or more parameters at the maximum ramp rate. For example, where themaximum ramp rate is 0.1 Volts per 400 milliseconds and IMD 106 repeatsthe operation of FIG. 11 every 100 milliseconds, IMD 106 adjusts avoltage amplitude by 0.025 Volts. Thus, IMD 106 performs four 0.025 Voltadjustments over 400 milliseconds, effectively ramping the voltageamplitude by 0.1 Volts over 400 milliseconds, e.g., the maximum ramprate.

Prior to delivering the electrical stimulation according to the one ormore adjusted parameters, one of IMD 106 and external programmer 104ensures that the one or more adjusted parameters are greater than thelower bound of the therapeutic window and less than the upper bound ofthe therapeutic window (1116). If the one or more adjusted parametersare less than the lower bound of the therapeutic window, one of IMD 106and external programmer 104 may reset the lower bound of the therapeuticwindow to be equal to the value of the one or more adjusted parameters.This may require user (e.g., clinician) input to allow this to occur.Alternatively, the adjusted parameter may be readjusted upward to thelower bound of the therapeutic window. If the one or more adjustedparameters are greater than the upper bound of the therapeutic window,one of IMD 106 and external programmer 104 may reset the upper bound ofthe therapeutic window to be equal to the value of the one or moreadjusted parameters. Again, this may require some type of input, such asinput from a clinician programmer providing approval from a clinician tooverrule the bound of the therapeutic window. Alternatively, theadjusted parameter may be readjusted downward to the upper bound of thetherapeutic window. In either case, the adjusted parameter is within thetherapeutic window or an adjusted therapeutic window. Upon determiningthat the one or more adjusted parameters are within the therapeuticwindow, IMD 106 delivers electrical stimulation according to the one ormore adjusted parameters (1118). After delivering the electricalstimulation, IMD 106 repeats the entire operation process and againsenses a signal of patient 112 (1102).

Upon determining that the sensed signal of patient 112 is not greaterthan the upper bound of the homeostatic window and the sensed signal isnot less than a lower bound of the homeostatic window, IMD 106 maintainsthe present magnitude of the one or more parameters (1108) and deliverselectrical stimulation according to the one or more adjusted parameters(1114). Thus, while the signal is within the upper and lower bounds ofthe homeostatic window, IMD 106 continues to deliver electricalstimulation at the present magnitude of the one or more parameters.Further, if the signal deviates outside of the homeostatic window, upondetecting that the signal has returned to the homeostatic window, IMD106 continues to deliver electrical stimulation at the previousmagnitude of the one or more parameters. After delivering the electricalstimulation, IMD 106 repeats the entire operation process and againsenses a signal of the brain 120 of patient 112 (1102).

FIG. 12 is a flowchart illustrating an example operation for adjustingthe homeostatic window in response to patient feedback according to thetechniques of the disclosure. For convenience, FIG. 12 is described withrespect to FIG. 1 .

In the example of FIG. 12 , external programmer 104 receives feedbackfrom patient 112 regarding the efficacy of electrical stimulationdelivered by IMD 106 (1202). For example, external programmer 104 mayreceive feedback from patient 112 that the electrical stimulationdelivered by IMD 106 is insufficient to control one or more symptoms ofpatient 112, or that the electrical stimulation delivered by IMD 106 iscausing side effects, paresthesia, or discomfort to patient 112.

In response to the feedback received from patient 112, externalprogrammer 104 determines an adjustment to the homeostatic window(1204). For example, if external programmer 104 receives feedback frompatient 112 that the electrical stimulation therapy is not treating theone or more symptoms of patient 112 effectively, external programmer 104may determine a downward adjustment of the upper bound of thehomeostatic window, or the entire homeostatic window itself. To drive aproportional signal (e.g., a neurological signal within the Betafrequency band) to a lower magnitude, the system increases the one ormore parameters of the electrical stimulation therapy, and therebyincreases the magnitude of electrical stimulation therapy to reduce thesymptoms of the patient. Alternatively, to drive an inverselyproportional signal (e.g., a neurological signal within the Gammafrequency band) to a lower magnitude, the system decreases the one ormore parameters of the electrical stimulation.

Similarly, if external programmer 104 receives feedback from patient 112that the electrical stimulation therapy is unpleasant, causes sideeffects, or is otherwise uncomfortable to patient 112, and if the signalis a proportional signal (e.g., a neurological signal within the Betafrequency band), external programmer 104 may determine an upwardadjustment of the lower bound of the homeostatic window, or the entirehomeostatic window itself. This has the effect of allowing theneurological signal to float to a higher window, effectively causing thesystem to decrease the one or more parameters of the electricalstimulation therapy, and thereby decreases the magnitude of electricalstimulation therapy to reduce side effects.

While the patient 112 may adjust one or more bounds of the homeostaticwindow, or the homeostatic window itself, typically, to ensure thesafety of the patient, the patient 112 may not alter the therapeuticwindow that sets lower and upper bounds for the one or more parametersof the electrical stimulation therapy. Thus, prior to performing theadjustment of the homeostatic window, external programmer 104 determineswhether the adjustment to the homeostatic window would result in astimulation parameter value that exceeds an upper bound of thetherapeutic window or is less than a lower bound of the therapeuticwindow (1206). Upon determining that the adjusted bounds of thehomeostatic window result in stimulation parameter values that arewithin the therapeutic window, external programmer performs theadjustment to the homeostatic window (1208).

FIG. 13 is a flowchart illustrating an example operation for adjustingthe homeostatic window in response to a signal indicative of aphysiological parameter of the patient according to the techniques ofthe disclosure. For convenience, FIG. 13 is described with respect toFIG. 1 .

In the example of FIG. 13 , external programmer 104 receives a signalfrom sensors 109, wherein the signal is indicative of a physiologicalparameter of the patient (1302). For example, in response to signalsfrom sensors 109, external programmer 104 may determine that themagnitude of one or more parameters defining the electrical stimulationtherapy is insufficient to reduce the one or more symptoms of patient112. In another example, in response to signals from sensors 109,external programmer 104 may determine that, based on a symptom of thepatient (e.g., tremor, rigidity, or wrist flexion), a posture of thepatient (e.g., laying, sitting, standing, etc.) or an activity level ofthe patient (i.e., sleeping, walking, exercising, etc.), externalprogrammer 104 should adjust the magnitude of one or more parametersdefining the electrical stimulation therapy.

In response to the signal received from sensors 109, external programmer104 determines an adjustment to the homeostatic window (1304). Forexample, external programmer 104 may determine an adjustment of theupper bound, the lower bound, or the entire homeostatic window itself.In one example, external programmer 104 makes an adjustment toeffectively increase magnitude of the electrical stimulation therapydelivered to patient 112 to further reduce the one or more symptoms ofthe patient. In another example, external programmer an adjustment toeffectively decrease magnitude of the electrical stimulation therapydelivered to patient 112 to reduce one or more side effects of theelectrical stimulation therapy delivered to patient 112.

Accordingly, in response to the signal received from sensors 109,external programmer 106 may shift the upper bound of the homeostaticwindow downward to decrease the magnitude of the signal required totrigger IMD 106 to ramp up the magnitude of the one or more parametersdefining the electrical stimulation to bring the signal back into thehomeostatic window. External programmer 106 may shift the upper bound tocause IMD 106 to respond more quickly to changes in the sensedneurological signal that may indicate that a larger magnitude of one ormore parameters of the electrical stimulation is required to reduce theone or more symptoms of patient 112. External programmer may adjust theupper bound of the homeostatic window in the opposite direction to havethe opposite effect. Similarly, external programmer 106 may shift thelower bound of the homeostatic window upward to increase the magnitudeof the sensed neurological signal required to trigger IMD 106 to rampdown the magnitude of the one or more parameters defining the electricalstimulation to bring the signal back into the homeostatic window.External programmer 106 may shift the lower bound to cause IMD 106 torespond more quickly to decreases in the sensed neurological signal thatmay indicate that a smaller magnitude of one or more parameters of theelectrical stimulation is required to avoid inducing side effects inpatient 112. External programmer may adjust the upper bound of thehomeostatic window in the opposite direction to have the oppositeeffect. External programmer may adjust the lower bound of thehomeostatic window in the opposite direction to have the oppositeeffect.

In yet a further example, external programmer 106 may adjust theposition of the entire homeostatic window to adjust both the magnitudeof the sensed neurological signal required to trigger IMD 106 to ramp upthe magnitude of the one or more parameters defining the electricalstimulation and the magnitude of the sensed neurological signal requiredto trigger IMD 106 to ramp down the magnitude of the one or moreparameters defining the electrical stimulation, so as to bring thesignal back into the homeostatic window. Thus, external programmer 106may adjust the shape and position of the homeostatic window so as todeliver adaptive DBS that is tailored to the needs of each individualpatient.

Typically, system 100 may not resize the therapeutic window beyondsafety guidelines set by the clinician, which may be expressed as amaximum adjustment to upper bound, lower bound, or window shift, eitherin an absolute sense or in the sense of a maximum adjustment per unittime. Thus, prior to performing the adjustment of the homeostaticwindow, external programmer 104 determines whether the adjustment to thehomeostatic window would result in a stimulation parameter that exceedsan upper bound of the therapeutic window or is less than a lower boundof the therapeutic window (1306). Upon determining that the adjustedbounds of the homeostatic window result in stimulation parameter valuesthat are within the therapeutic window, external programmer performs theadjustment to the homeostatic window (1308).

FIG. 14 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation according to the techniques of thedisclosure. For convenience, FIG. 14 is described with respect to IMD106 of FIG. 2 .

In one example, stimulation generator 202 of IMD 106 generateselectrical stimulation therapy (1402). Processor 210 of IMD 106,delivers the electrical stimulation therapy to tissue of a patient 112via electrodes 116, 118 (1404). During delivery of the electricalstimulation therapy, processor 210, via electrodes 116, 118, senses asignal of the patient 112. In some examples, this signal is a signal ofpatient 112, such as a neurological signal within the Beta frequencyband or Gamma frequency band of the brain 120 of patient 112. In otherexamples, this signal is a physiological parameter signal from one ormore sensors, such as one or more accelerometers, gyros, ormagnetometers. In this example, the signal may indicate a physiologicalparameter of the patient 112, such as a magnitude of rigidity of thepatient due to Parkinson's disease, a magnitude of tremor of the patientdue to Parkinson's disease, a magnitude of wrist flexion of the patient,a posture of the patient, a physical activity level of the patient, or asleep state of the patient.

In response to the signal, processor 210 adjusts a magnitude of at leastone parameter of the electrical stimulation therapy such that a sensedsignal of the patient is not less than a lower bound of a homeostaticwindow and not greater than an upper bound of a homeostatic window(1406). In some examples, the sensed signal is a neurological signalwithin the Beta frequency band or Gamma frequency band of a brain 120 ofpatient 112. For example, while a patient is not taking medicationselected to reduce one or more symptoms, a clinician determines aminimum magnitude of one or more parameters defining the electricalstimulation therapy, such as a minimum voltage or current amplitude,sufficient to reduce the one or more symptoms. The clinician defines theupper bound of the homeostatic window as a magnitude of the signal ofthe patient at this magnitude of electrical stimulation. Further, theclinician may determine a minimum magnitude of one or more parametersdefining the electrical stimulation therapy, such as a minimum voltageor current amplitude, sufficient to reduce or maintain reduction of oneor more symptoms when the patient is taking medication selected toreduce the symptoms. The clinician defines a lower bound of thehomeostatic window as the signal of the patient at this magnitude ofstimulation.

FIG. 15 is a graph illustrating an example response of a signal of abrain of the patient to electrical stimulation in accordance with thetechniques of the disclosure. For convenience, FIG. 15 is described withrespect to FIG. 1 . In the example of FIG. 15 , the horizontal axisdepicts frequency in Hertz, while the vertical axis depicts a magnitude(e.g., spectral noise density) of a sensed neurological signal asmeasured in microvolts per root-Hertz. In the example of FIG. 15 , theelectrical stimulation further comprises a frequency of 140 Hertz and apulse width of 90 microseconds.

In some examples, neurological signals of brain 120 of patient 112 maydemonstrate multiple peak magnitudes within a frequency band of sensedneurological signals. Each of these peak magnitudes may be locatedwithin a different sub-band of the frequency band. Further, each ofthese sub-bands may respond differently to the electrical stimulation.In examples of system 100 where electrical stimulation is deliveredbased on sensing or tracking a neurological signal of brain 120 ofpatient 112, the correlation of the neurological signal to the severityof symptoms in the patient may depend on which sub-band of frequenciesof the neurological signal is selected to define the electricalstimulation.

As an example of the above, patient 112 suffers from Parkinson's diseaseand may exhibit symptoms such as rigidity and tremor. Further, brain 120of patient 112 exhibits two or more peak magnitudes (e.g., a multi-modalpeak) of activity within a single Beta-frequency band. In this example,a first peak magnitude exists within a first sub-band of the Betafrequency band, while a second peak magnitude exists within a secondsub-band of the Beta frequency band. Further, in response to electricalstimulation therapy, the first peak magnitude displays minimalsuppression or reduction in magnitude, while the second peak magnitudedisplays a large amount of suppression or reduction in magnitude. Inother words, the first peak magnitude may require electrical stimulationof a much higher magnitude to reduce the first peak magnitude to acertain amount, while the second peak magnitude may require electricalstimulation having much less magnitude to reduce the second peakmagnitude to the same amount.

In this example, patient 112 receives electrical stimulation therapy tosuppress rigidity and/or tremor due to Parkinson's disease. Whilereceiving the electrical stimulation therapy, the change in severity ofthe patient's rigidity and tremor has been shown to correlate most tochanges in the first peak magnitude within the first sub-band of theBeta frequency band, and correlate least to changes in the second peakmagnitude within the second sub-band of the Beta frequency band. Inother words, the change in severity of the patient's rigidity and tremormay correlate most strongly to the peak magnitude within the sub-band ofthe Beta frequency band that changes the least in response to electricalstimulation therapy (e.g., the peak magnitude that requires the highestlevel of electrical stimulation therapy to suppress), in comparison toother peak magnitudes within other sub-bands of the Beta frequency thatfluctuate greatly in response to electrical stimulation.

Thus, the techniques of the disclosure describe how system 100 mayselect a sub-band of frequencies for use as a control signal forcontrolling electrical stimulation such that the electrical stimulationtherapy that IMD 102 delivers correlates more accurately to the severityof the symptoms of patient 112. Furthermore, such a sub-band offrequencies may be used to accurately define the bounds of a homeostaticwindow as described above. For example, system 100 may select thesub-band of frequencies that demonstrates the least response toelectrical stimulation, as that sub-band has been found to exhibitgreater correlation to the severity of the symptoms of patient 112 thanother sub-bands that exhibit greater response to electrical stimulation.

For example, as depicted in the example of FIG. 15 , IMD 106 delivers,via electrodes 116, 118 disposed along leads 114, electrical stimulationat a plurality of voltage amplitudes to brain 120 of patient 112. In theexample of FIG. 15 , IMD 106 delivers a plurality of electricalstimulation therapies at various voltage amplitudes. Further, IMD 106senses, via electrodes 116, 118 disposed along leads 114, a response oflocal field potentials of neurological signals located within a betafrequency band of about 13 Hertz to about 30 Hertz of brain 120 ofpatient 112.

The response of the sensed neurological signal of brain 120 of patient112 to each electrical stimulation therapy is depicted in FIG. 15 . Forexample, when IMD 102 delivers no electrical stimulation, the sensedneurological signal exhibits a baseline response 1501. For example, whenIMD 102 delivers electrical stimulation comprising a voltage amplitudeof 1 Volt, the sensed neurological signal exhibits a first response1502. Further, when IMD 102 delivers electrical stimulation comprising avoltage amplitude of 2 Volts, the sensed neurological signal exhibits asecond response 1503. When IMD 102 delivers electrical stimulationcomprising a voltage amplitude of 2.5 Volts, the sensed neurologicalsignal exhibits a third response 1504. When IMD 102 delivers electricalstimulation comprising a voltage amplitude of 3 Volts, the sensedneurological signal exhibits a fourth response 1505. When IMD 102delivers electrical stimulation comprising a voltage amplitude of 3.5Volts, the sensed neurological signal exhibits a fifth response 1506.

As depicted in the example of FIG. 15 , the neurological signals locatedwithin the beta frequency band exhibit two peaks. A first peak lieswithin a first sub-band 1510 of frequencies of the beta band, at about13 Hertz to about 22 Hertz, and centered at about 15 Hertz. A secondpeak lies within a second sub-band 1520 of frequencies of the beta band,at about 23 Hertz to about 28 Hertz, and centered at about 25 Hertz. Asfurther depicted in FIG. 15 , as the voltage amplitude of the electricalstimulation increases, the magnitude of the signals within firstsub-band 1510 of frequencies diminish relatively slightly, while themagnitude of the signals within second sub-band 1520 of frequenciesdiminish relatively greatly. Thus, in accordance with the techniques ofthe disclosure, first sub-band 1510 may be selected as a control signalfor controlling one or more parameters defining the electricalstimulation because first sub-band 1510 exhibits less responsiveness toelectrical stimulation therapy then second sub-band 1520.

Similarly, first sub-band 1510 may be used to define the bounds of ahomeostatic window as described above. For example, as described above,while the patient is not taking medication selected to reduce one ormore symptoms, a clinician determines a minimum magnitude of one or moreparameters defining the electrical stimulation therapy, such as aminimum voltage amplitude or minimum current amplitude, sufficient toreduce the one or more symptoms. The clinician defines the upper boundof the homeostatic window as a magnitude of the first sub-band 1510 ofthe patient at this magnitude of the electrical stimulation therapy.Further, the clinician may determine a minimum magnitude of one or moreparameters defining the electrical stimulation therapy, such as aminimum voltage amplitude or minimum current amplitude, sufficient toreduce or maintain reduction of one or more symptoms when the patient istaking medication selected to reduce the symptoms. The clinician definesa lower bound of the homeostatic window as a magnitude of the firstsub-band 1510 of the patient at this magnitude of stimulation.

While the example of FIG. 15 depicts only two peak magnitudes within thebeta frequency band, it is recognized that other patients may have threeor more peak magnitudes, and therefore three or more sub-bands offrequencies that may be selected as a control signal for controlling oneor more parameters defining the electrical stimulation or to define thehomeostatic window. In such an example, the sub-band of the three ormore sub-bands of frequencies that exhibits the least responsiveness toelectrical stimulation therapy may be selected as the control signal forcontrolling the electrical stimulation therapy.

Furthermore, while in the example of FIG. 15 , the responsiveness of thesensed neurological signal to variations in voltage amplitude of theelectrical stimulation is determined, the techniques of the disclosurerecognize that other types of parameters defining the electricalstimulation may be varied to select a sub-band of frequencies. Forexample, a selection of one or more electrodes for delivery of theelectrical stimulation, a polarity of the one or more selectedelectrodes, a current amplitude (for a current-controlled system), anelectrical stimulation pulse width, an electrical stimulation pulsefrequency, or any combination of the above may be used to select asub-band of frequencies for use as a control signal for controlling oneor more parameters defining the electrical stimulation or to define thehomeostatic window.

FIG. 16 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation according to the techniques of thedisclosure. Specifically, FIG. 16 depicts an example operation forselecting a neurological signal within a sub-band of frequencies for useas a control signal for controlling electrical stimulation or to definethe bounds of a homeostatic window. FIG. 16 is described with respect toFIG. 1 for convenience. As described above, in some examples,neurological signals of brain 120 of patient 112 demonstrate multiplepeak magnitudes within a frequency band of sensed neurological signals.Each of these peak magnitudes may be located within a different sub-bandof the frequency band, e.g., the beta band. Further, each of thesesub-bands may respond differently to electrical stimulation.

IMD 106 delivers, via electrodes 116, 118 disposed along leads 114,electrical stimulation to brain 120 of patient 112 (1602). Further, IMD106 senses, via electrodes 116, 118 disposed along leads 114, a responseof neurological signals located within a frequency band of brain 120 ofpatient 112, e.g., in terms of a voltage amplitude of the neurologicalsignals. In one example, the frequency band is a Beta frequency band ofabout 13 Hertz to about 30 Hertz.

While delivering the electrical stimulation, IMD 106 determines a firstresponse of a first sensed neurological signal to the electricalstimulation (1604). Further, IMD 106 determines a second response of asecond sensed neurological signal to the electrical stimulation (1606).In some examples, the first sensed neurological signal is within a firstsub-band of frequencies of the frequency band of brain 120 of patient112. In one example, the first sensed neurological signal is within afirst sub-band of Beta-band frequencies of about 13 Hertz to about 30Hertz, the first sub-band comprising frequencies of about 13 Hertz toabout 22 Hertz. In some examples, the first sensed neurological signalcomprises neurological signals at about 15 Hertz. In some examples, thesecond sensed neurological signal is within a second sub-band offrequencies of the frequency band of brain 120 of patient 112, andcomprises frequencies that are different from the first sub-band offrequencies. In one example, the frequencies of the second sub-band aregreater than the frequencies of the first sub-band. In one example, thesecond sensed neurological signal is within a second sub-band ofBeta-band frequencies from about 13 Hertz to about 30 Hertz, the secondsub-band comprising frequencies of about 23 Hertz to about 28 Hertz. Insome examples, the second sensed neurological signal comprisesneurological signals at about 25 Hertz.

IMD 106 selects, based on the respective response to the electricalstimulation, one of the first sensed signal and the second sensed signalfor use as a control signal for controlling the electrical stimulation,or to define bounds of a homeostatic window, such as described above(1608). For example, IMD 106 determines a first magnitude of suppressionof a first magnitude of the first sensed signal in response toelectrical stimulation therapy. Further, IMD 106 determines a secondmagnitude of suppression of a second magnitude of the second sensedsignal in response to electrical stimulation therapy. In this example,IMD 106 compares the first magnitude with the second magnitude todetermine which, of the first sensed signal and the second sensedsignal, demonstrates less response to the electrical stimulation. IMD106 selects the one of the first sensed signal and the second sensedsignal that demonstrates the least response to the electricalstimulation for use as a control signal for controlling the electricalstimulation, or to define bounds of a homeostatic window. As discussedabove, the sensed signal that demonstrates the least suppression inresponse to electrical stimulation may more accurately indicate to theseverity of symptoms of a patient than another sensed signal thatdemonstrates greater suppression in response to electrical stimulation.

Subsequently, IMD 106 adjusts at least one parameter of the electricalstimulation therapy based on the selected signal (e.g., the first sensedsignal in the above example) (1610). For example, as magnitude of thefirst sensed signal increases, IMD 106 increases at least one parameterdefining the electrical stimulation therapy, such as a voltage amplitude(for a voltage-controlled system) or a current amplitude (for acurrent-controlled system). As another example, as the magnitude of thefirst sensed signal decreases, IMD 106 decreases at least one parameterdefining the electrical stimulation therapy. In this fashion, IMD 106may provide adaptive DBS to patient 112 based on the first sensed signalto suppress one or more symptoms of patient 112 in proportion to theseverity of the one or more systems while ensuring that the first sensedsignal correlates strongly to the severity of the one or more symptoms.

FIG. 17 is a graph illustrating measured neurological signal of a brain120 of patient 112 during movement by patient 112. For convenience, FIG.17 is described with respect to FIG. 1 . The horizontal axis of FIG. 17depicts frequency in Hertz, and the vertical axis depicts magnitude ofthe sensed neurological signal (e.g., a spectral power) in microvoltsper root-Hertz. As described above, in some examples, neurologicalsignals of brain 120 of patient 112 may demonstrate multiple peakmagnitudes within a frequency band of sensed neurological signals. Eachof these peak magnitudes may be located within a different sub-band ofthe frequency band. While each of these sub-bands may responddifferently to the electrical stimulation, as described above, each ofthese sub-bands may further demonstrate different amounts of movementdesynchronization during to movement by patient 112. Movementdesynchronization refers to the phenomenon where neurological signalswithin brain 120 of patient 112 display a reduction in magnitude duringmovement by patient 112. Different neurological signals within the brainmay exhibit different amounts of movement desynchronization. Forexample, movement by patient 112 may cause a first peak magnitude withina first sub-band to substantially decrease, while the same movement maycause a second peak magnitude within a second sub-band to decrease onlyslightly relative to the peak magnitude of the signal in the firstsub-band. In other words, during a patient movement, a first peakmagnitude in the first sub-band of the signal may decrease more than asecond peak magnitude in a second sub-band of the signal, relative torespective peak magnitudes in the absence of patient movement. In thiscase, the first peak magnitude in the first sub-band exhibits a greateramount movement desynchronization than the second peak magnitude in thesecond sub-band, e.g., of the beta band.

In examples of system 100 where electrical stimulation is deliveredbased on sensing or tracking a neurological signal of brain 120 ofpatient 112, the correlation of the neurological signal to the severityof symptoms in patient 112, and thus the effectiveness of the electricalstimulation therapy, may depend on which sub-band of frequencies of theneurological signal is selected to define the electrical stimulation.For example, if a first sub-band is selected as a control signal forcontrolling electrical stimulation, and that first sub-band demonstratesa large amount of movement desynchronization, movement of patient 112may be correlated with a suppression of signals within the firstsub-band. This may cause IMD 106 to incorrectly reduce the magnitude ofone or more parameters of electrical stimulation delivered to patient112 despite the fact that patient 112 may require the higher magnitudeof the one or more parameters of electrical stimulation to effectivelysuppress one or more symptoms of a disease of patient 112. For example,as a patient suffering from rigidity due to Parkinson's disease moves,magnitude of signals in a beta-frequency band of neurological signalsmay diminish, causing IMD 106 to decrease electrical stimulation,resulting in degradation in limb movement of the patient. Thus, thetechniques of the disclosure describe how system 100 may select asub-band of frequencies for use as a control signal for controllingelectrical stimulation such that the electrical stimulation therapy thatIMD 102 delivers correlates more accurately to the severity of thesymptoms of patient 112, regardless of movement by patient 112.Furthermore, such a sub-band of frequencies may be used to accuratelydefine the bounds of a homeostatic window as described above. Forexample, system 100 may select the sub-band of frequencies thatdemonstrates the least suppression during movement, relative to othersub-bands in a selected band (e.g., the beta band), as that sub-band hasbeen found to exhibit greater correlation to the severity of thesymptoms of patient 112 than other sub-bands that exhibit greatersuppression during movement.

For example, as depicted in the example of FIG. 17 , IMD 106 delivers,via electrodes 116, 118 disposed along leads 114, electrical stimulationtherapy to patient 112 to suppress rigidity and tremor due toParkinson's disease. IMD 106 senses, via electrodes 116, 118 disposedalong leads 114, a magnitude of neurological signals located within aBeta frequency band of about 13 Hertz to about 30 Hertz of brain 120 ofpatient 112. IMD 106 records a first magnitude 1701 of neurologicalsignals within the Beta frequency band sensed while patient 112 is atrest. Further, IMD 106 records a second magnitude 1702 of neurologicalsignals within the Beta frequency band sensed while patient 112 isperforming a walking forward exercise (WFE). As depicted in FIG. 17 ,upon performing the walking forward exercise, neurological signalswithin the Beta frequency experience movement desynchronization. This isdemonstrated as a suppression of the neurological signals within theBeta frequency band, e.g., of about 13 Hertz to about 33 Hertz. Movementdesynchronization may particularly be observable for frequencies in thesub-band range of about 10 Hertz to about 25 Hertz. However, thespecific frequencies of such movement desynchronization may be uniquefor each patient and may lie anywhere within a range of about 13 Hertzto about 33 Hertz. In the example of FIG. 17 , a first sub-band offrequencies centered around 25 Hertz and a second sub-band offrequencies centered around 15 Hertz may be suitable for use as controlsignals for controlling delivery of electrical stimulation.

In the example of FIG. 17 , IMD 106 may select the first sub-band offrequencies centered around 25 Hertz as the control signal forcontrolling the electrical stimulation or for use in defining ahomeostatic window, because the first sub-band of frequencies centeredaround 25 Hertz depict a minimal amount of change due to movement bypatient 112. In contrast, IMD 106 may not select the second sub-band offrequencies centered around 15 Hertz as a control signal for controllingelectrical stimulation or for use in defining a homeostatic window,because the second sub-band of frequencies centered around 15 Hertzdemonstrates a large amount of movement desynchronization.

However, the specific region of suppression due to movementdesynchronization may be different from patient to patient. Thus, if asub-band of frequencies exhibiting a large amount of movementdesynchronization is used as a control signal, when patient 112 moves,the control signal reduces due to movement desynchronization, causingIMD 106 to incorrectly reduce electrical stimulation when patient 112still requires electrical stimulation. Accordingly, by selecting asub-band of frequencies that demonstrates minimal movementdesynchronization for use as a control signal for controlling electricalstimulation or for use in defining a homeostatic window, system 100ensures that the control signal more accurately relates to the severityof the symptoms of patient 112. Additionally, system 100 may furtherensure the control signal accurately relates to the severity of thesymptoms of patient 112 by selecting threshold settings for thehomeostatic window, as described above, that take into accountsuppressed neurological signals due to movement by the patientassociated with desynchronization. Furthermore, system 100 may furtherensure the control signal accurately relates to the severity of thesymptoms of patient 112 by selecting a ramp rate (e.g., a rate ofchange) of the one or more parameters of the electrical stimulation thatare less susceptible to changes in the neurological signal caused byshort-term movements associated with desynchronization.

While the example of FIG. 17 depicts only two peak magnitudes within thebeta frequency band, it is recognized that other patients may have threeor more peak magnitudes, and therefore three or more sub-bands offrequencies that may be selected as a control signal for controlling oneor more parameters defining the electrical stimulation or to define thehomeostatic window. In such an example, the sub-band of the three ormore sub-bands of frequencies exhibits the least amount of movementdesynchronization may be selected as the control signal for controllingthe electrical stimulation therapy.

Alternatively, or in addition, upon determining a change in magnitude ofneurological signals within a frequency band, system 100 may adjust theramp time (e.g., the rate of change) of one or more parameters of theelectrical stimulation therapy. For example, in a fast-ramping system(e.g., a system where one or more parameters of the electricalstimulation are adjusted at time steps less than one second), upondetermining that a Beta frequency band of patient 112 is susceptible tomovement desynchronization, IMD 106 may decrease a rate of change of theone or more parameters of the electrical stimulation therapy. Inalternate examples, upon detecting a movement of patient 112 related toa Beta frequency band desynchronization, such as walking, IMD 106 maydecrease the rate of change of the one or more parameters of theelectrical stimulation therapy while the movement is detected. Infurther examples, a rate of change of the one or more parameters of theelectrical stimulation therapy is selected such that the one or moreparameters of the electrical stimulation remains constant for a durationof the movement of patient 112. Further, when defining the bounds of ahomeostatic window as described above, the lower limit of the at leastone parameter is defined such that IMD 106 ramps up the one or moreparameters of the electrical stimulation, even when a movement ofpatient 112 causes Beta frequency band desynchronization. As oneexample, in a current-controlled system, a current amplitude isincreased from zero to a maximum current selected from a range of about1.3 milliamps to about 2.0 milliamps over a time period selected fromabout 250 milliseconds to about 1 second. As another example, in avoltage-controlled system, a voltage amplitude is increased from zero toa maximum voltage selected from a range of about 2 volts to about 3volts over a time period selected from about 250 milliseconds to about 1second.

In further examples, upon detecting movement associated withdesynchronization, IMD 106 may switch from a fast-ramping system to aslow-ramping system (e.g., a system where one or more parameters of theelectrical stimulation are adjusted at time steps greater than onesecond). In other words, during normal operation, IMD 106 may adjust theone or more parameters of the electrical stimulation at a rate greaterthan once per second. Upon detecting movement associated withdesynchronization, IMD 106 decreases the ramp rate such that IMD 106adjusts the one or more parameters of the electrical stimulation at arate less than once per second.

As a further example, in a slow-ramping system, IMD 106 may deliveradaptive electrical stimulation therapy that tracks on- and off-phasesof medication administered to patient 112 to reduce one or more symptomsof patient 112. For example, patient 112 may suffer from Parkinson'sdisease and take medication administered to suppress dyskinesia andimprove longevity. Such medication may both suppress the symptoms ofdyskinesia in patient 112, and also suppress neurological signals withina Beta frequency band of brain 120 of patient 112. The effects of suchmedication on patient 1112 may not show effects for about 30 minutesafter dosage, and the medication may gradually reach its full strengthover a wash-in period of about 10 minutes. Similarly, as the medicationwears off, the effects of the medication in suppressing dyskinesia mayalso gradually diminish.

Accordingly, system 100 may adjust the rate of change of the one or moreparameters of the electrical stimulation therapy more slowly such thatthe one or more parameters of the electrical stimulation is increased atapproximately the same rate as the medication wash-in period (e.g., theperiod of time between when the patient takes the medication and themedication reaches full strength). As one example, in acurrent-controlled system, a current amplitude is increased from zero toa maximum current selected from a range of about 1.3 milliamps to about2.0 milliamps over a time period selected from about 10 minutes to about30 minutes. Such a time period may be set by the clinician and based onthe wash-in period of a specific medication taken by the patient. Asanother example, in a voltage-controlled system, a voltage amplitude isincreased from zero to a maximum voltage selected from a range of about2 volts to about 3 volts over a time period selected from about 10minutes to about 30 minutes. Such a time period may also be set by theclinician and based on the wash-in period of a specific medication takenby the patient. Such a ramp rate may allow IMD 106 to track changes in abeta frequency band of patient 112 due to medication. Further, such aramp rate may allow IMD 106 to avoid periods of desynchronization in theBeta frequency band due to movements of patient 112 that are expected tobe less than 10 minutes in duration.

Furthermore, while in the example of FIG. 17 , examples are providedwherein a ramp rate of one of current amplitude or voltage amplitude isadjusted, the techniques of the disclosure recognize that other types ofparameters defining the electrical stimulation may be adjusted as afunction of the amount of movement desynchronization displayed by thesensed neurological signal. For example, a ramp rate of one or more of:a selection of one or more electrodes for delivery of the electricalstimulation, a polarity of the one or more selected electrodes, acurrent amplitude (for a current-controlled system), an electricalstimulation pulse width, an electrical stimulation pulse frequency, orany combination of the above may be adjusted.

FIG. 18 is a flowchart illustrating an example operation for deliveringadaptive deep brain stimulation according to the techniques of thedisclosure. Specifically, FIG. 18 depicts an example operation forselecting a neurological signal within a sub-band of frequencies for useas a control signal for controlling electrical stimulation or to definethe bounds of a homeostatic window. FIG. 18 is described with respect toFIG. 1 for convenience. As described above, in some examples,neurological signals of brain 120 of patient 112 demonstrate multiplepeak magnitudes within a frequency band of sensed neurological signals.Each of these peak magnitudes may be located within a different sub-bandof the frequency band. Further, each of these sub-bands may expressdiffering amounts of desynchronization during movement of patient 112.

IMD 106 delivers, via electrodes 116, 118 disposed along leads 114,electrical stimulation to brain 120 of patient 112 (1802). Further, IMD106 senses, via electrodes 116, 118 disposed along leads 114, amagnitude of neurological signals located within a frequency band ofbrain 120 of patient 112. In one example, the frequency band is a Betafrequency band of about 13 Hertz to about 30 Hertz.

While delivering the electrical stimulation, IMD 106 determines a firstmagnitude of a first sensed neurological signal during movement by thepatient (1804). Further, IMD 106 senses a second magnitude of a secondsensed neurological signal during the movement by the patient (1806). Insome examples, the first sensed neurological signal is within a firstsub-band of frequencies of the frequency band of brain 120 of patient112. In one example, the first sensed neurological signal is within afirst sub-band of Beta-band frequencies of about 13 Hertz to about 30Hertz, the first sub-band comprising frequencies of about 13 Hertz toabout 22 Hertz. In some examples, the first sensed neurological signalcomprises neurological signals within the first sub-band at about 15Hertz. In some examples, the second sensed neurological signal is withina second sub-band of frequencies of the frequency band of brain 120 ofpatient 112, and comprises frequencies that are different from the firstsub-band of frequencies. In one example, the second sensed neurologicalsignal is within a second sub-band of Beta-band frequencies, the secondsub-band comprising frequencies of about 23 Hertz to about 28 Hertz. Insome examples, the second sensed neurological signal comprisesneurological signals is in the second sub-band at about 25 Hertz.

IMD 106 selects, based on the respective magnitude during the movementof the patient, the one of the first sensed signal and the second sensedsignal for use as a control signal for controlling the electricalstimulation, or to define bounds of a homeostatic window, such asdescribed above (1808). For example, IMD 106 determines a firstmagnitude of suppression of a first magnitude of the first sensed signalduring the movement of the patient. Further, IMD 106 determines a secondmagnitude of suppression of a second magnitude of the second sensedsignal during the movement of the patient. In this example, IMD 106compares the first magnitude with the second magnitude to determinewhich, of the first sensed signal and the second sensed signal,demonstrates a lesser change, e.g., lesser change in magnitude duringthe movement of the patient. IMD 106 selects the one of the first sensedsignal and the second sensed signal that demonstrates the least changeduring the movement of the patient for use as a control signal forcontrolling the electrical stimulation, or to define bounds of ahomeostatic window. As discussed above, by using the sensed signal thatdemonstrates the least suppression during movement of the patient,system 100 may mitigate circumstances where system 100 detects asuppression of the neurological signal caused by movement, incorrectlyinterpreting the suppression as a reduced need by patient 112 for theelectrical stimulation therapy, and responding by reducing the one ormore parameters of the electrical stimulation.

Subsequently, IMD 106 adjusts at least one parameter of the electricalstimulation therapy based on the selected signal (e.g., the first sensedsignal in the above example) (1810). For example, as magnitude of thefirst sensed signal increases, IMD 106 increases at least one parameterdefining the electrical stimulation therapy, such as a voltage amplitude(for a voltage-controlled system) or a current amplitude (for acurrent-controlled system). As another example, as magnitude of thefirst sensed signal decreases, IMD 106 decreases at least one parameterdefining the electrical stimulation therapy. Alternatively, IMD 106 mayadjust a rate of change of the at least one parameter defining theelectrical stimulation therapy, as described above. In this fashion, IMD106 may provide adaptive DBS to patient 112 based on the first sensedsignal to suppress one or more symptoms of patient 112 in proportion tothe severity of the one or more systems while ensuring that aneurological signal selected as a control signal for the electricalstimulation is selected such that the control signal is robust tomovement desynchronization.

As an example, IMD 106 may use the first sensed signal to define thebounds of a homeostatic window as described above. For example, asdescribed above, while the patient is not taking medication selected toreduce one or more symptoms, a clinician determines a minimum magnitudeof one or more parameters defining the electrical stimulation therapy,such as a minimum voltage amplitude or minimum current amplitude,sufficient to reduce the one or more symptoms. The clinician defines theupper bound of the homeostatic window as a magnitude of the first sensedsignal of the patient at this magnitude of the electrical stimulationtherapy. Further, the clinician may determine a minimum magnitude of oneor more parameters defining the electrical stimulation therapy, such asa minimum voltage amplitude or minimum current amplitude, sufficient toreduce or maintain reduction of one or more symptoms when the patient istaking medication selected to reduce the symptoms. The clinician definesa lower bound of the homeostatic window as a magnitude of the firstsensed signal of the patient at this magnitude of stimulation.Subsequently, IMD 106 delivers electrical stimulation to the patient,and may adjust one or more parameters defining the electricalstimulation within a parameter range defined by the lower and upperbounds of the therapeutic window based on the activity of the firstsensed signal within the homeostatic window.

The techniques described in this disclosure may be implemented, at leastin part, in hardware, software, firmware or any combination thereof. Forexample, various aspects of the described techniques may be implementedwithin one or more processors, such as fixed function processingcircuitry and/or programmable processing circuitry, including one ormore microprocessors, digital signal processors (DSPs), applicationspecific integrated circuits (ASICs), field programmable gate arrays(FPGAs), or any other equivalent integrated or discrete logic circuitry,as well as any combinations of such components. The term “processor” or“processing circuitry” may generally refer to any of the foregoing logiccircuitry, alone or in combination with other logic circuitry, or anyother equivalent circuitry. A control unit comprising hardware may alsoperform one or more of the techniques of this disclosure.

Such hardware, software, and firmware may be implemented within the samedevice or within separate devices to support the various operations andfunctions described in this disclosure. In addition, any of thedescribed units, modules or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

The techniques described in this disclosure may also be embodied orencoded in a computer-readable medium, such as a computer-readablestorage medium, containing instructions. Instructions embedded orencoded in a computer-readable storage medium may cause a programmableprocessor, or other processor, to perform the method, e.g., when theinstructions are executed. Computer readable storage media may includerandom access memory (RAM), read only memory (ROM), programmable readonly memory (PROM), erasable programmable read only memory (EPROM),electronically erasable programmable read only memory (EEPROM), flashmemory, a hard disk, a CD-ROM, a floppy disk, a cassette, magneticmedia, optical media, or other computer readable media.

Various examples have been described. These and other examples arewithin the scope of the following claims.

What is claimed is:
 1. A method for delivering electrical stimulationtherapy to a patient, the method comprising: delivering electricalstimulation therapy to tissue of a patient via electrodes; and adjustinga level of at least one parameter of the electrical stimulation therapysuch that a sensed signal indicative of a gamma signal of a brain of thepatient is not less than a lower bound and not greater than an upperbound of a range; wherein the upper bound is one of: a magnitude of thesensed signal while receiving a first level of the electricalstimulation therapy that is a minimum level sufficient to reduce one ormore symptoms of a disease and while the patient is receiving medicationfor reduction of one or more symptoms of the disease or disorder; or amagnitude of the sensed signal while receiving a second level of theelectrical stimulation therapy sufficient to cause maximum reduction ofthe one or more symptoms of the disease or disorder without inducingsubstantial side effects in the patient and while the patient is notreceiving the medication for reduction of the one or more symptoms ofthe disease; and wherein the lower bound is one of: a magnitude of thesensed signal while receiving a third level of the electricalstimulation therapy that is a minimum level sufficient to reduce the oneor more symptoms of the disease and while the patient is not receivingthe medication for reduction of the one or more symptoms of the disease;or a magnitude of the sensed signal while receiving a fourth level ofthe electrical stimulation therapy, while the patient is not receivingthe medication for reduction of the one or more symptoms of the disease,that is sufficient to reduce the one or more symptoms of the disease ordisorder but which above the level, substantially no further substantialreduction in the one or more symptoms is achieved.
 2. The method ofclaim 1, wherein the upper bound is the magnitude of the sensed signalwhile receiving the first level of the electrical stimulation therapythat is the minimum level sufficient to reduce the one or more symptomsof the disease and while the patient is receiving the medication forreduction of the one or more symptoms of the disease.
 3. The method ofclaim 1, wherein the upper bound is the magnitude of the sensed signalwhile receiving the second level of the electrical stimulation therapysufficient to cause maximum reduction of the one or more symptoms of thedisease or disorder without inducing substantial side effects in thepatient and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease.
 4. The method ofclaim 1, wherein the lower bound is the magnitude of the sensed signalwhile receiving the third level of the electrical stimulation therapythat is the minimum level sufficient to reduce the one or more symptomsof the disease and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease.
 5. The method ofclaim 1, wherein the lower bound is the magnitude of the sensed signalwhile receiving the fourth level of the electrical stimulation therapy,while the patient is not receiving the medication for reduction of theone or more symptoms of the disease, that is sufficient to reduce theone or more symptoms of the disease or disorder but which above thelevel, substantially no further substantial reduction in the one or moresymptoms is achieved.
 6. The method of claim 1, further comprisingadjusting, in response to a patient input, at least one of the magnitudeof the lower bound or the magnitude of the upper bound.
 7. The method ofclaim 1, further comprising: determining, on a periodic basis, anaverage magnitude of the at least one parameter of the electricalstimulation therapy; and while delivering the electrical stimulationtherapy, increasing the level of the at least one parameter of theelectrical stimulation therapy by a bias level.
 8. The method of claim7, wherein the at least one parameter of the electrical stimulationtherapy is a voltage amplitude, and wherein the bias level of thevoltage amplitude of the electrical stimulation therapy is selected froma range of about 0.1 Volts to about 5 Volts.
 9. The method of claim 7,wherein the at least one parameter of the electrical stimulation therapyis a current amplitude, and wherein the bias level of the currentamplitude of the electrical stimulation therapy is selected from a rangeof about 0.1 milliamps to about 5 milliamps.
 10. The method of claim 1,wherein the gamma signal of the brain of the patient is within afrequency band of about 35 Hertz to about 200 Hertz.
 11. An implantablemedical device (IMD) comprising: stimulation generation circuitryconfigured to deliver electrical stimulation therapy to tissue of apatient via electrodes; and processing circuitry configured to adjust alevel of at least one parameter of the electrical stimulation therapysuch that a sensed signal indicative of a gamma signal of a brain of thepatient is not less than a lower bound and not greater than an upperbound of a range; wherein the upper bound is one of: a magnitude of thesensed signal while receiving a first level of the electricalstimulation therapy that is a minimum level sufficient to reduce one ormore symptoms of a disease and while the patient is receiving medicationfor reduction of one or more symptoms of the disease or disorder; or amagnitude of the sensed signal while receiving a second level of theelectrical stimulation therapy sufficient to cause maximum reduction ofthe one or more symptoms of the disease or disorder without inducingsubstantial side effects in the patient and while the patient is notreceiving the medication for reduction of the one or more symptoms ofthe disease; and wherein the lower bound is one of: a magnitude of thesensed signal while receiving a third level of the electricalstimulation therapy that is a minimum level sufficient to reduce the oneor more symptoms of the disease and while the patient is not receivingthe medication for reduction of the one or more symptoms of the disease;or a magnitude of the sensed signal while receiving a fourth level ofthe electrical stimulation therapy, while the patient is not receivingthe medication for reduction of the one or more symptoms of the disease,that is sufficient to reduce the one or more symptoms of the disease ordisorder but which above the level, substantially no further substantialreduction in the one or more symptoms is achieved.
 12. The IMD of claim11, wherein the upper bound is the magnitude of the sensed signal whilereceiving the first level of the electrical stimulation therapy that isthe minimum level sufficient to reduce the one or more symptoms of thedisease and while the patient is receiving the medication for reductionof the one or more symptoms of the disease.
 13. The IMD of claim 11,wherein the upper bound is the magnitude of the sensed signal whilereceiving the second level of the electrical stimulation therapysufficient to cause maximum reduction of the one or more symptoms of thedisease or disorder without inducing substantial side effects in thepatient and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease.
 14. The IMD ofclaim 11, wherein the lower bound is the magnitude of the sensed signalwhile receiving the third level of the electrical stimulation therapythat is the minimum level sufficient to reduce the one or more symptomsof the disease and while the patient is not receiving the medication forreduction of the one or more symptoms of the disease.
 15. The IMD ofclaim 11, wherein the lower bound is the magnitude of the sensed signalwhile receiving the fourth level of the electrical stimulation therapy,while the patient is not receiving the medication for reduction of theone or more symptoms of the disease, that is sufficient to reduce theone or more symptoms of the disease or disorder but which above thelevel, substantially no further substantial reduction in the one or moresymptoms is achieved.
 16. The IMD of claim 11, wherein the processingcircuitry is further configured to: determine, on a periodic basis, anaverage magnitude of the at least one parameter of the electricalstimulation therapy; and while delivering the electrical stimulationtherapy, increase the level of the at least one parameter of theelectrical stimulation therapy by a bias level.
 17. The IMD of claim 16,wherein the at least one parameter of the electrical stimulation therapyis a voltage amplitude, and wherein the bias level of the voltageamplitude of the electrical stimulation therapy is selected from a rangeof about 0.1 Volts to about 5 Volts.
 18. The IMD of claim 16, whereinthe at least one parameter of the electrical stimulation therapy is acurrent amplitude, and wherein the bias level of the current amplitudeof the electrical stimulation therapy is selected from a range of about0.1 milliamps to about 5 milliamps.
 19. The IMB of claim 11, wherein anexternal programmer determines the upper bound and the lower bound. 20.A medical device system comprising: one or more sensors; an implantablemedical device (1 MB) comprising stimulation generation circuitryconfigured to deliver electrical stimulation therapy to tissue of apatient via electrodes; and processing circuitry configured to adjust alevel of at least one parameter of the electrical stimulation therapysuch that a sensed signal indicative of a gamma signal of a brain of thepatient is not less than a lower bound and not greater than an upperbound of a range; wherein the upper bound is one of: a magnitude of thesensed signal while receiving a first level of the electricalstimulation therapy that is a minimum level sufficient to reduce one ormore symptoms of a disease and while the patient is receiving medicationfor reduction of one or more symptoms of the disease or disorder; or amagnitude of the sensed signal while receiving a second level of theelectrical stimulation therapy sufficient to cause maximum reduction ofthe one or more symptoms of the disease or disorder without inducingsubstantial side effects in the patient and while the patient is notreceiving the medication for reduction of the one or more symptoms ofthe disease; and wherein the lower bound is one of: a magnitude of thesensed signal while receiving a third level of the electricalstimulation therapy that is a minimum level sufficient to reduce the oneor more symptoms of the disease and while the patient is not receivingthe medication for reduction of the one or more symptoms of the disease;or a magnitude of the sensed signal while receiving a fourth level ofthe electrical stimulation therapy, while the patient is not receivingthe medication for reduction of the one or more symptoms of the disease,that is sufficient to reduce the one or more symptoms of the disease ordisorder but which above the level, substantially no further substantialreduction in the one or more symptoms is achieved.